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Sample records for single intravenous administration

  1. Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

    PubMed

    Bianco, A W; Constable, P D; Cooper, B R; Taylor, S D

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses. PMID:26416348

  2. Pharmacokinetics of enrofloxacin in horses after single intravenous and intramuscular administration.

    PubMed

    Kaartinen, L; Panu, S; Pyörälä, S

    1997-09-01

    Pharmacokinetic behaviour of enrofloxacin was studied in 6 horses after intravenous (i.v.) or intramuscular (i.m.) administration of enrofloxacin (5 mg/kg bwt). Concentration of enrofloxacin and ciproflaxin were measured by high performance liquid chromatography in serum. Antimicrobial activity of the samples was determined with an agar-diffusion technique. Reactions at the site of i.m. injection were monitored clinically and by determination of serum creatine kinase (CK) activity. After i.v. administration, elimination half-life of enrofloxacin was 4.4 h and volume of distribution was 2.3 1/kg bwt. Enrofloxacin was rapidly metabolised to ciprofloxacin. The half-life of ciprofloxacin parallelled that of the parent drug, its concentration in serum reached 20-35% of that of the parent drug. After i.m. administration, elimination half-life of enrofloxacin was longer (9.9 h) than after i.v. administration. Mean absorption time of enrofloxacin was also long (9.9 h). No statistically significant differences were found when half-life and mean residence time of antimicrobial activity were compared with those of enrofloxacin and ciprofloxacin from chemically analysed data. Intramuscular injection of enrofloxacin was found to be very irritating. After i.m. administration, CK activity in serum, compared with pre-injection levels, increased over 10-fold. CK activity also stayed high during the 32 h follow-up period. Clinical reactions, such as swelling or tenderness at the i.m. injection sites, were observed in 2 horses. PMID:9306065

  3. The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

    PubMed

    Rumpler, M J; Colahan, P; Sams, R A

    2014-02-01

    A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration. PMID:23859819

  4. Excretion of Morroniside in Rat Urine After Single Oral and Intravenous Administration.

    PubMed

    Xiong, Shan; Li, Jinglai; Zhang, Zhenqing

    2016-07-01

    This study was designed to develop a sensitive, simple and rapid method for the quantitation of morroniside in rat urine using high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) and to investigate the excretion of morroniside in rat urine. The mobile phase consisted of water-acetonitrile (gradient elution) at a flow rate of 0.4 mL/min. Detection was performed using positive-ion electrospray ionization in multiple reaction monitoring (MRM) modes. And the detection of morroniside in rat urine by the LC-MS-MS was accurate and precise from 1.0 to 2,500 ng/mL (a correlation coefficient of 0.9953). The recoveries and matrix effects were all in line with the biological sample measurement requirements. The intraday accuracy was 88.68-105.78% with precision of 6.50-11.19% and the interday accuracy was 95.77-102.43% with precision of 7.08-10.40%. Excretion data of morroniside in rat urine indicated that 21.43‰ (i.g.) and 100.35% (i.v.) of the dose administered was excreted as unconverted form, respectively. And the maximal excretion rate was 27.57 and 482.42 μg/h after oral and intravenous administration, respectively. These results indicated that the developed method has satisfactory sensitivity, accuracy and precision for the quantification of morroniside in rat urine. PMID:26896349

  5. Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs.

    PubMed

    Zhang, Wei; Huo, Shi-Xia; Wen, Yan-Li; Xing, Han; Zhang, Qing; Li, Ning; Zhao, Di; Sun, Xiao-Lin; Xu, Jie; Yan, Ming; Chen, Xi-Jing

    2015-08-01

    Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use. PMID:26253497

  6. Phenylbutazone in racing greyhounds: plasma and urinary residues 24 and 48 hours after a single intravenous administration.

    PubMed

    Mills, P C; Ng, J C; Skelton, K V; Seawright, A A; Auer, D E

    1995-08-01

    The concentrations of phenylbutazone (PBZ), oxyphenbutazone (OPBZ) and gammahydroxyphenylbutazone (OHPBZ) in plasma and urine from 50 Greyhounds 24 and 48 h after the intravenous administration of a single dose of PBZ (30 mg/kg) were measured. The 24 h plasma concentrations of OPBZ and OHPBZ, the 48 h plasma concentration of OHPBZ and the 24 h urinary concentration of PBZ were normally distributed, while log transformations were required before the 24 h plasma concentration of PBZ and the 24 and 48 h urinary concentrations of OPBZ and OHPBZ became normally distributed. The 95%, 99%, 99.9% and 99.99% upper predicted confidence intervals for both 24 h and 48 h plasma and urinary concentrations demonstrated wide potential variation in the concentration of the analytes should PBZ be administered to Greyhounds. The 24 h plasma and urinary concentrations of PBZ were weakly correlated, but no similar relationship existed for OPBZ or OHPBZ. The urinary concentrations of each analyte were not affected by the trainer or sex of the Greyhound or the urinary pH. We conclude that it would be impossible to predict the timing of the PBZ administration or the plasma concentration of PBZ from the measurement of the concentration of PBZ in a single sample of urine. PMID:8579562

  7. Tolerability and pharmacokinetics of biapenem following single and multiple intravenous administrations in healthy Chinese subjects: an open-label, randomized, single-center study.

    PubMed

    Liu, Y; Li, Z; Yang, C; Zheng, H; Lv, Y; Chen, H; Zhang, Y; Shi, S

    2013-08-01

    This study was designed to evaluate the tolerability and pharmacokinetics of biapenem after single and multiple intravenous administrations in healthy Chinese subjects. Subjects were randomly allocated to receive a single 0.15, 0.3, or 0.6 g dose of biapenem. Subjects assigned to the 0.3 g single dose group continued into the multiple-dose phase. Blood samples were collected over 6 h and plasma biapenem concentrations were determined by a validated HPLC method. Tolerability was assessed by monitoring vital signs, laboratory parameters, physical examinations, electrocardiogram, and adverse events collected by non-directive questioning/spontaneous reporting. Pharmacokinetic parameters for biapenem after intravenous administration of a single dose of 0.15, 0.3, or 0.6 g were as follows: Cmax=7.06 (1.30), 15.59 (1.33), and 29.12 (1.22) mg/L; AUC0-6 h=8.95 (1.33), 22.62 (1.25), and 42.05 (1.19) mg · h/L; t1/2=0.97 (0.13), 1.04 (0.08), and 1.12 (0.08) h; CL=15.78 (1.32), 12.91 (1.24), and 13.95 (1.19) L/h; Vd=21.87 (1.25), 19.31 (1.25), and 22.41 (1.23) L, respectively. Pharmacokinetic parameters for biapenem after intravenous administration of multiple 0.3 g doses were as follows: Cmax=18.50 (1.16) mg/L; AUC0-6 h=26.45 (1.15) mg · h/L; t1/2=1.06 (0.15) h; CL=11.06 (1.16) L/h; Vd=16.78 (1.19) L. The incidence of reported AEs was as follows: phlebitis (2/10), nausea (1/10), and diarrhea (1/10). All of the AEs were mild in intensity. The pharmacokinetic properties of biapenem were linear at dose of 0.15-0.6 g. All biapenem doses appeared to be well tolerated. PMID:23585303

  8. Integration of pharmacokinetic and pharmacodynamic indices of orbifloxacin in beagle dogs after a single intravenous and intramuscular administration.

    PubMed

    Gebru, Elias; Lee, Joong-Su; Chang, Zhi-Qiang; Hwang, Mi-Hyun; Cheng, Henrique; Park, Seung-Chun

    2009-07-01

    The pharmacokinetics (PK) and pharmacodynamics (PD) of orbifloxacin were studied in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 2.5 mg/kg body weight. An absolute bioavailability of 100.1% +/- 4.76%, a terminal half-life of 4.23 +/- 0.2 h and 3.95 +/- 0.15 h after i.v. and i.m. administration, a steady-state volume of distribution of 1.61 +/- 0.13 liters/kg, and clearance of 0.31 +/- 0.03 liters/h/kg were observed. Orbifloxacin showed rapid, concentration-dependent killing against the Escherichia coli, Staphylococcus aureus, Staphylococcus intermedius, and Proteus mirabilis clinical isolates. Computations based on PK-PD analysis indicated that the recommended dose is unlikely to be clinically effective against some strains like S. intermedius. Therefore, a higher dose of orbifloxacin would be worthy of consideration for treatment of certain bacterial infections in dogs. PMID:19398644

  9. Integration of pharmacokinetic and pharmacodynamic indices of valnemulin in broiler chickens after a single intravenous and intramuscular administration.

    PubMed

    Zhao, Dong-Hao; Zhou, Yu-Feng; Yu, Yang; Shi, Wei; Yang, Xue; Xiao, Xia; Deng, Hui; Qiao, Guilin Gary; Fang, Bing-Hu; Liu, Ya-Hong

    2014-07-01

    The antibacterial efficacy of valnemulin against Staphylococcus aureus was studied ex vivo in broiler chickens after intravenous and intramuscular administration at a dose of 10 mg/kg bodyweight (BW). The minimum inhibitory concentrations (MICs) of valnemulin against S. aureus strains ATCC 25923 in broth and serum were 0.12 and 1 µg/mL, respectively. The MIC50 and MIC90 of valnemulin against all susceptible S. aureus strains isolated from chickens in the test population were 0.06 and 0.12 μg/mL, respectively. Protein binding, which greatly influences the efficacy of valnemulin, was assayed by equilibrium dialysate in vitro. A high binding fraction of 86.2% was found, which seems in good agreement with the difference of bacterial susceptibility tests observed in broth and serum. The surrogate index of AUC0-24/MIC required for the lowest bacteriostatic effect, and 2 log10CFU reduction in bacterial count were 24.4 h and 38.0 h, respectively. The required daily dose of valnemulin for a bacteriostatic activity was calculated to be 15 mg/kg BW based on the MIC90 of 0.12 µg/mL. Considering the slow disposition process of valnemulin and an AUC0-24 h value of more than 10-fold obtained from diseased animals, a suggested dose of 3 mg/kg BW is sufficient to achieve a satisfactory therapeutic efficacy in infected broilers. Due to the time-dependent antibacterial characteristics of valnemulin, the recommended daily dose should be split into two or three sub-doses to achieve the highest effectiveness while diminishing the risk of development of bacterial resistance. PMID:24906499

  10. Disinfection practices in intravenous drug administration.

    PubMed

    Helder, Onno K; Kornelisse, René F; Reiss, Irwin K M; Ista, Erwin

    2016-06-01

    The aim of the study was to determine the effectiveness of a feedback intervention on adherence to disinfection procedures during intravenous medication preparation and administration. We found that full adherence to the protocols significantly improved from 7.3% to 21.5% (P < .001) regarding medication preparation and from 7.9% to 15.5% (P = .012) regarding medication administration. However, disinfection practices still need improvement. PMID:26899528

  11. Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Guzman, David Sanchez-Migallon; KuKanich, Butch; Drazenovich, Tracy L.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

    2014-01-01

    Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

  12. Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Sanchez-Migallon Guzman, David; KuKanich, Butch; Drazenovich, Tracy L.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

    2014-01-01

    Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

  13. Population Pharmacokinetics of High-dose Methotrexate After Intravenous Administration in Chinese Osteosarcoma Patients from a Single Institution

    PubMed Central

    Zhang, Wei; Zhang, Qing; Tian, Xiaohuang; Zhao, Haitao; Lu, Wei; Zhen, Jiancun; Niu, Xiaohui

    2015-01-01

    Background: High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition. Methods: An intravenous HD-MTX solution (10 g/m2) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained. Results: The following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1)i = CL1TV × [1- θCL1 −MTXNUM × MTXNUM]×[1-θCL1 −CrCI1 × (CrCl1 −1.89)]×eηCL1i (L/h). V1 (central volume): (V1)i = V1TV × eηV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV ×[1- θCL2 −BODYAREA × (bodyarea − 1.62)]×eηCL2i (L/h). V2(peripheral compartment): (V2)i = V2TV ×[1 − θV2−bodyarea × (bodyarea-1.62)]× eηV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a

  14. An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis.

    PubMed

    Wiesholzer, Martin; Pichler, Petra; Reznicek, Gottfried; Wimmer, Michaela; Kussmann, Manuel; Balcke, Peter; Burgmann, Heinz; Zeitlinger, Markus; Poeppl, Wolfgang

    2016-05-01

    The objective of this study was to determine the pharmacokinetic profile of meropenem in automated peritoneal dialysis (APD) patients. In 6 patients without peritonitis, a single dose of 0.5 g of meropenem was applied intraperitoneally (i.p.) or intravenously (i.v.) and concentrations in serum and dialysate were measured at specified intervals over 24 h with high-performance liquid chromatography-mass spectrometry. The mean maximum concentrations of meropenem in serum (Cmax) were 27.2 mg/liter (standard deviation [SD], ±6.9) and 10.1 mg/liter (SD, ±2.5) and in dialysate were 3.6 mg/liter (SD, ±2.3) and 185.8 mg/liter (SD, ±18.7) after i.v. and i.p. administrations, respectively. The mean areas under the curve from 0 to 24 (AUC0-24) of meropenem in serum were 173.5 mg · h/liter (SD, ±29.7) and 141.4 mg · h/liter (SD, ±37.5) (P = 0.046) and in dialysate were 42.6 mg · h/liter (SD, ±20.0) and 623.4 mg · h/liter (SD, ±84.1) (P = 0.028) after i.v. and i.p. administrations, respectively. The ratios for dialysate exposure over plasma exposure after i.v. and i.p. treatments were 0.2 (SD, ±0.1) and 4.6 (SD, ±0.9), respectively (P = 0.031). A mean target value of 40% T>MIC (time for which the free meropenem concentration exceeds the MIC) for clinically relevant pathogens with EUCAST susceptibility breakpoints of 2 mg/liter was reached in serum after i.p. and i.v. administrations and in dialysate after i.p. but not after i.v. administration. The present data indicate that low i.p. exposure limits the i.v. use of meropenem for PD-associated peritonitis. In contrast, i.p. administration not only results in superior concentrations in dialysate but also might be used to treat systemic infections. PMID:26902765

  15. Methylprednisolone pharmacokinetics after intravenous and oral administration.

    PubMed Central

    Al-Habet, S M; Rogers, H J

    1989-01-01

    1. The pharmacokinetics of methylprednisolone (MP) were studied in five normal subjects following intravenous doses of 20, 40 and 80 mg methylprednisolone sodium succinate (MPSS) and an oral dose of 20 mg methylprednisolone as 4 x 5 mg tablets. Plasma concentrations of MP and MPSS were measured by both high performance thin layer (h.p.t.l.c.) and high pressure liquid chromatography (h.p.l.c.). 2. The mean values (+/- s.d.) of half-life, mean residence time (MRT), systemic clearance (CL) and volume of distribution at steady state (Vss) of MP following intravenous administration were 1.93 +/- 0.35 h, 3.50 +/- 1.01 h, 0.45 +/- 0.12 lh-1 kg-1 and 1.5 +/- 0.63 1 kg-1, respectively. There was no evidence of dose-related changes in these values. The plasma MP concentration-time curves were superimposable when normalized for dose. 3. The bioavailability of methylprednisolone from the 20 mg tablet was 0.82 +/- 0.11 (s.d.). 4. In vivo hydrolysis of MPSS was rapid with a half-life of 4.14 +/- 1.62 (s.d.) min, and was independent of dose. In contrast, in vitro hydrolysis in plasma, whole blood and red blood cells was slow; the process continuing for more than 7 days. Sodium fluoride did not prevent the hydrolysis of MPSS. PMID:2655680

  16. Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration.

    PubMed

    Rawlins, M D; Henderson, D B; Hijab, A R

    1977-04-20

    Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose. PMID:862649

  17. Pharmacokinetics of cephalexin in calves after intravenous and subcutaneous administration.

    PubMed

    Garg, S K; Chaudhary, R K; Srivastava, A K

    1996-01-01

    The pharmacokinetics of cephalexin was investigated in male calves following a single intravenous (i.v.) and subcutaneous (s.c.) administration (10 mg/kg). The distribution rate constant and distribution half-life were 3.34 +/- 1.22 h-1 and 0.32 +/- 0.08 h, respectively. The values of elimination half-lives following i.v. and s.c. administration were 3.17 +/- 1.30 and 2.56 +/- 0.24 h, respectively. The absorption half-life following s.c. administration was 0.09 +/- 0.01 h. The apparent volume of distribution was 0.65 +/- 0.16 and 0.46 +/- 0.07 L/kg and total body clearance was 2.96 +/- 0.46 and 1.66 +/- 0.31 ml/kg/min, respectively, following i.v. and s.c. administration. Systemic availability following subcutaneous administration was found to be almost complete (103.08%). The satisfactory intravenous dosage regimen of cephalexin for calves would be 11.3 mg/kg as the priming dose followed by 10.0 mg/kg as the maintenance dose to be repeated at 6-h intervals. However, the subcutaneous dosage regimen of cephalexin in calves would be 8.0 mg/kg followed by 7.05 mg/kg at 8-h intervals. PMID:8908743

  18. Plasma atropine concentrations via intravenous, endotracheal, and intraosseous administration.

    PubMed

    Prete, M R; Hannan, C J; Burkle, F M

    1987-03-01

    To date, there have been limited studies on the pharmacokinetics of intravenous atropine and no pharmacokinetic studies on the endotracheal or intraosseous administration of atropine. This study examines the time to peak plasma concentration of atropine following intravenous, endotracheal, and intraosseous administration in anesthetized monkeys using a triple crossover design. Plasma atropine was assayed by a radioreceptor method. The time to peak plasma concentration of atropine was shortest with intravenous administration; and longest with endotracheal administration. The mean plasma concentration of atropine was significantly higher in intravenous administrations than in endotracheal administrations at 0.75 and 2 minutes; compared to that noted in intraosseous administrations, the concentration was significantly higher only at 0.75 minutes. The mean plasma concentration of atropine administered intraosseously was significantly higher than that of endotracheal administrations at 5 minutes and was greater than that of intravenous and endotracheal administrations for the samples collected from 5 to 30 minutes. The endotracheal and intraosseous routes provide alternatives to the intravenous administration of atropine when intravenous access is limited or not available. PMID:3828010

  19. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination

    PubMed Central

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-01-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl®). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4–16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. PMID:24666477

  20. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    PubMed

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. PMID:24666477

  1. Intravenous Medication Administration in Intensive Care: Opportunities for Technological Solutions

    PubMed Central

    Moss, Jacqueline; Berner, Eta; Bothe, Olaf; Rymarchuk, Irina

    2008-01-01

    Medication administration errors have been shown to be frequent and serious. Error is particularly prevalent in highly technical specialties such as critical care. The purpose of this study was to describe the characteristics of intravenous medication administration in five intensive care units. These data were used within the context of a larger study to design information system decision support to decrease medication administration errors in these settings. Nurses were observed during the course of their work and their intravenous medication administration process, medication order source, references used, calculation method, number of medications prepared simultaneously, and any interruptions occurring during the preparation and delivery phases of the administration event were recorded. In addition, chart reviews of medication administration records were completed and nurses were asked to complete an anonymous drop-box questionnaire regarding their experiences with medication administration error. The results of this study are discussed in terms of potential informatics solutions for reducing medication administration error. PMID:18998790

  2. Chronic cannulation for intermittent intravenous fluid administration.

    PubMed

    Mostardi, R A; Worsencroft, D; Stern, J; Vanessen, F

    1975-04-01

    A system is described for rapid and effective venous cannulation for long-term administration of fluids in rabbits. This method is completely free of any harness or sling-type apparatus and in no way interferes with the normal mobility of the animal. The animals maintained in this way have participated in programs of tri-weekly administration (2-3 ml/dose) of fluid for as long as 5 mo. PMID:1141108

  3. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

    PubMed Central

    Nagelschmitz, J; Blunck, M; Kraetzschmar, J; Ludwig, M; Wensing, G; Hohlfeld, T

    2014-01-01

    Background The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Methods Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing. PMID:24672263

  4. Purple glove syndrome: a dreadful complication of intravenous phenytoin administration

    PubMed Central

    Lalla, Rakesh; Malhotra, Hardeep Singh; Garg, Ravindra Kumar; Sahu, Ritesh

    2012-01-01

    Purple glove syndrome is an uncommon but dreaded complication of intravenous phenytoin administration characterised by pain, oedema and purple-blue discolouration of the limb distal to the site of injection. We describe a 37-year-old gentleman having the characteristic purple glove appearance after phenytoin loading, and discuss the salient features of this syndrome highlighting the pathophysiological and preventive aspects. PMID:22922927

  5. Quantitative determination of particulate contamination in intravenous administration sets.

    PubMed

    Di Paolo, E R; Hirschi, B; Pannatier, A

    1990-10-19

    Particle counts were performed on 1,000 intravenous administration sets from ten suppliers on the Swiss market using a HIAC/Royco electronic counter. The following main conclusions may be drawn from the results of this study: --the small particles were the most numerous, regardless of the type of set; --the differences in the counts obtained for the different suppliers' sets tended to level off for particles larger than 10 microns; --the drip chamber and latex connector may be two important sources of particles; --the particulate contamination from the sets is relatively low compared with the amount of particles contained in the parenteral solutions. PMID:2255588

  6. Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration.

    PubMed Central

    Cochrane, S M; Black, W D; Parent, J M; Allen, D G; Lumsden, J H

    1990-01-01

    Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat. PMID:2306662

  7. Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10mg/kg) of intravenous i.v.) or oral administration in freshwater at a mean water temperature of 25.4°C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography...

  8. Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.

    PubMed Central

    Escudero, E; Espuny, A; Vicente, S; Cárceles, C M

    1999-01-01

    The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio. PMID:9918330

  9. Pharmacokinetics of ibuprofen enantiomers in rats after intravenous and oral administration of ibuprofen arginate.

    PubMed

    Wang, Xiao-Lin; Han, Jing; Zhang, Dan; Liu, Hui-Chen

    2012-01-01

    The pharmacokinetics of ibuprofen enantiomers were studied in rats after intravenous and oral administration of ibuprofen arginate by means of a chiral HPLC method. The pharmacokinetics of ibuprofen was stereoselective after intravenous and oral administration of ibuprofen arginate. The pharmacokinetic stereoselectivity was higher after oral administration than that after intravenous administration. The systematic (R)-(-)-to-(S)-(+) inversion might be more important than the presystematic one in the stereoselective pharmacokinetics after oral administration. Oral administration of ibuprofen arginate resulted in a very rapid absorption of (S)-(+)-ibuprofen (eutomer), and the absolute bioavailabilities of (S)-(+)-ibuprofen and (R)-(-)-ibuprofen were about 100% and 80%, respectively. Based on the systemic exposure of (S)-(+)-ibuprofen, it could be concluded that the pharmacological actions might be similar when ibuprofen arginate was given orally and intravenously, except some differences in the onset of action. PMID:22493811

  10. Pharmacokinetics of TDP223206 following intravenous and oral administration to intact rats and intravenous administration to bile duct-cannulated rats.

    PubMed

    Chen, Yanmin; Cheng, Deping; Marugan, Juan Jose; Manthey, Carl; Tomczuk, Bruce; Huebert, Norman

    2008-05-01

    The pharmacokinetics of TDP223206 was studied following single intravenous and oral administrations in rats. A mixture of TDP223206 and (14)C-TDP223206 were administered to intact and bile duct-cannulated rats. Following intravenous administration, plasma concentrations declined biphasically. The AUC(inf) increased linearly with dose but was not dose proportional. The PK parameters of TDP223206 indicated low clearance (254-386 ml/h/kg) and a moderate volume of distribution (968-1883 ml/kg). The bioavailability was 32.95% and 24.46% for 10 and 50 mg/kg oral doses, respectively. (14)C-TDP223206 was distributed widely into different tissues with small intestine, liver, kidneys and large intestine having large tissue to plasma ratios. (14)C-TDP223206 was the major circulating component in the plasma. A total of 91.2% of administered radioactivity of (14)C-TDP223206 was recovered in bile indicating that biliary excretion was the major pathway for drug elimination. (14)C-TDP223206-acyl glucuronides were the major metabolites in bile. The oxo-(14)C-TDP223206 was the major metabolite in plasma and an important metabolite in bile. Two forms of diastereomeric acyl glucuronides of (14)C-TDP223206 were detected in bile with similar LC/MS intensities suggesting a similar biotransformation capacity. Only one form of these (14)C-TDP223206-acyl glucuronides was detected in plasma suggesting that enterohepatic recirculation was related to the nature of the stereo-isomers. PMID:18260095

  11. Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats.

    PubMed

    LeVine, Dana N; Papich, Mark G; Gookin, Jody L; Davidson, Gigi S; Davis, Jennifer L; Hayes, Rebecca B

    2011-04-01

    Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats. PMID:21239199

  12. Safety, tolerability, and pharmacokinetics of oral and intravenous administration of GSK1322322, a peptide deformylase inhibitor.

    PubMed

    Naderer, Odin J; Jones, Lori S; Zhu, John; Kurtinecz, Milena; Dumont, Etienne

    2013-11-01

    GSK1322322 is the first in a new class of antibiotics that targets peptide deformylase (PDF), an essential bacterial enzyme required for protein maturation. This randomized, double-blind, placebo-controlled, eight-cohort phase I trial enrolled 62 healthy volunteers to assess safety, tolerability, and pharmacokinetic profiles of GSK1322322. GSK1322322 was administered as a single oral or intravenous (IV) dose, escalating from 500 to 3,000 mg or repeat IV doses escalating from 500 to 1,500 mg twice daily. Upon repeat IV administration, GSK1322322 exhibits linear pharmacokinetics over time upon repeat doses as shown by time-invariant pharmacokinetics. A dose-proportional increase in area under concentration-time curve was observed after single or repeat IV dosing, whereas clearance at steady state remained generally unchanged across doses. There was minimal accumulation of GSK1322322 after repeat IV twice-daily administration. After oral tablet doses of GSK1322322 1,000 and 1,500 mg, absolute bioavailability was 69% and 56%, respectively. GSK1322322 administration at single and repeat IV doses and at supratherapeutic single IV doses of 2,000 and 3,000 mg was associated with mild-to-moderate drug-related adverse events. On the basis of the pharmacokinetics and tolerability demonstrated in this study, GSK1322322 has the potential to become the first-in-class PDF inhibitor for clinical use. PMID:23907665

  13. Administration of Intravenous Inf liximab for Prevention of Peritoneal Adhesions Formation in Rats

    PubMed Central

    Nikeghbalian, Saman; Vafaei, Homeira; Moradian, Farid; Kazemi, Kourosh; Tanideh, Nader; Shayan, Leila; Nikeghbalian, Zahra

    2015-01-01

    Objectives: To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. Methods: This was an experimental study being performed in animal laboratory of Shiraz University of Medical Sciences during 2012. Sixty albino rats were randomly assigned in to three groups by Random Design Method. The first group received single infliximab injection (n=20), the second one received double infliximab injection (n=20) and the third received nothing (n=20), after receiving intra-peritoneal injection of talc for induction of peritoneal adhesions. All the animals were sacrificed after 6 weeks and the peritoneal adhesions were evaluated according to Nair classification. Results: We observed that the mean adhesion grade was lower in those who received double dose of infliximib when compared to single dose and controls. However the difference did not reach a significant value (p=0.178). The grade of peritoneal adhesion was also comparable between the three study groups (p=0.103). The mean number of 1st WBC count was also comparable between three study groups (p=0.382). We observed that 2nd WBC count was also comparable between two study groups (p=0.317). Conclusion: Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat. PMID:27162911

  14. The effect of preoperative intravenous paracetamol administration on postoperative fever in pediatrics cardiac surgery

    PubMed Central

    Abdollahi, Mohammad-Hasan; Foruzan-nia, Khalil; Behjati, Mostafa; Bagheri, Babak; Khanbabayi-Gol, Mehdi; Dareshiri, Shahla; Pishgahi, Alireza; Zarezadeh, Rafie; Lotfi-Naghsh, Nazgol; Lotfi-Naghsh, Ainaz; Naghavi-Behzad, Mohammad

    2014-01-01

    Background: Post-operative fever is a common complication of cardiac operations, which is known to be correlated with a greater degree of cognitive dysfunction 6 weeks after cardiac surgery. The aim of the present study was to examine efficacy and safety of single dose intravenous Paracetamol in treatment of post-operative fever in children undergoing cardiac surgery. Materials and Methods: In this randomised, double-blind, placebo-controlled clinical trial, 80 children, aged 1-12 years, presenting for open heart surgery were entered in the trial and randomly allocated into two groups: Placebo and Paracetamol. After induction of anaesthesia, 15 mg/kg intravenous Paracetamol solution was infused during 1 h in the Paracetamol group. Patients in placebo group received 15 mg/kg normal saline infusion during the same time. Since the end of operation until next 24 h in intensive care unit, axillary temperature of the two group patients was recorded in 4-h intervals. Any fever that occurred during this period had been treated with Paracetamol suppository (125 mg) and the amount of antipyretic drug consumption for each patient had been recorded. In order to examine the safety of Paracetamol, patients were evaluated for drug complication at the same time. Results: Mean axillary temperature during first 24 h after operation was significantly lower in Paracetamol group compared with placebo group (P = 0.001). Overall fever incidence during 24 h after operation was higher in placebo group compared with Paracetamol group (P = 0.012). Of Paracetamol group patients, 42.5% compared with 15% of placebo group participants had no consumption of antipyretic agent (Paracetamol suppository) during 24 h after operation (P = 0.001). Conclusion: This study suggests that single dose administration of intravenous Paracetamol before paediatric cardiac surgeries using cardiopulmonary bypass; reduce mean body temperature in the first 24 h after operation. PMID:25298601

  15. Preparation of intravenous drug administration guidelines for a pediatric intensive care unit.

    PubMed

    Manrique-Rodríguez, Silvia; Sánchez-Galindo, Amelia; Fernández-Llamazares, Cecilia M; López-Herce, Jesús; Rodríguez-Gómez, Milagrosa; Echarri-Martínez, Lara; Carrillo-Álvarez, Angel; Sanjurjo-Sáez, María

    2014-01-01

    Drug administration is one of the main sources of errors in pediatric intensive care units (PICUs). An available guide for intravenous drug administration might be useful. The aim of this article is to present the methodology and results for the development of a guide for intravenous drug administration in a PICU. A total of 116 drugs were included. Standard concentrations, diluents, technique for reconstitution and dilution, stability, rate of administration, and relevant observations were defined for each drug according to a review of the most commonly used literature resources. The main unique feature of this article is that it includes standard concentrations for each drug. PMID:24384883

  16. Pharmacokinetics and tissue distribution of spinosin after intravenous administration in rats.

    PubMed

    Li, Yu-Juan; Dai, Yue-Han; Yu, Ye-Ling; Li, Yan; Deng, Yu-Lin

    2007-08-01

    Spinosin is the major effective single constituent in the traditional Chinese herb Semen Ziziphi Spinosae, which is used for sedation and hypnosis. For the further use of spinosin in treating insomnia, the pharmacokinetics and tissue distribution of spinosin after intravenous administration to rats was investigated. An HPLC method with an ODS column (250 mm x 4.6 mm, i.d.) and a mobile phase of acetonitrile-water-acetic acid (23:77:1) was used for the determination of spinosin in the plasma and tissues of rats. Vanillin was used as an internal standard, and spinosin was detected at 334 nm. The calibration curve of spinosin in plasma showed good linearity over the concentration range of 1-300 microg/ml, and the quantitation of limit of plasma was 1 microg/ml. The linear range of concentrations of spinosin in the heart, spleen, stomach, lung, testis, brain, and intestine was 0.1-40 microg/ml and the quantitation limit was 0.1 microg/ml. The linear range of concentrations of spinosin in the liver and kidney was 1-150 microg/ml, and the quantitation limit was 1 microg/ml. The correlation coefficients of all calibration curves were between 0.9939 and 0.9980. The intra and interrun precision for all samples was less than < or =11.0%. The time-concentration curve of spinosin after the intravenous administration of a single dose of 20 mg/kg to rats corresponded to the two-compartment model. The main pharmacokinetic parameters T(0.5alpha), T(0.5beta), CLs, AUC(0-T), and V(c) were 6.66 min, 51.5 min, 1.42 l.min(-1), 2.83 mg.min.ml(-1), and 14.0 l.kg(-1), respectively. At 20 min, a concentration peak occurred in liver and brain tissues. The highest level of spinosin occurred in the liver, followed by the spleen and kidney. The lowest level of spinosin appeared in the testis, followed by the brain. Spinosin was not detected in smooth and skeletal muscle. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo. PMID

  17. Incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant

    PubMed Central

    Lundberg, Jordan D.; Crawford, Brooke Sorgen; Phillips, Gary; Berger, Michael J.; Wesolowski, Robert

    2014-01-01

    Purpose Fosaprepitant is known to cause infusion-site reactions. However, there is limited data regarding these reactions including the effect of peripheral intravenous administration or other potential factors on their incidence. This single-institution retrospective study was undertaken to investigate the incidence of infusion-site reactions with single-dose intravenous (IV) fosaprepitant when given through a peripheral line prior to administration of chemotherapy. Risk factors for the development of infusion-site reactions with fosaprepitant were also explored. Methods Medical records of patients with cancer receiving IV fosaprepitant through a peripheral line were reviewed. The primary objective of this study was to estimate the incidence of infusion-site reactions at our institution. Data collection included demographics, fosaprepitant infusion information, and grading of reactions. Results We found a 15 % incidence of infusion-site reactions among all peripherally administered doses of fosaprepitant. The 50 reactions occurred in 43 unique patients representing an incidence per patient of 28.7 % (43/150; 95 % confidence interval (CI) 21.6–36.6). Factors found to be associated with infusion-site reactions included age [odds ratio (OR) 0.97 (95 % CI 0.94–0.99)], location of IV line [OR forearm vs. hand 0.41 (95% CI 0.20–0.85); OR antecubital fossa vs. hand 0.31 (95 % CI 0.11–0.87)], and simultaneous maintenance IV fluid rate ≥100 mL/h during fosaprepitant infusion [OR 0.19 (95 % CI 0.08–0.44)]. Conclusions The incidence of infusion-site reactions with peripherally administered fosaprepitant as seen in this study is higher than that reported in the package insert. Risk factors for developing infusion-site reactions in our patient population include age, location of IV line, and simultaneous maintenance IV fluid rate of <100 mL/h. PMID:24402412

  18. Pharmacokinetics of Uridine Following Ocular, Oral and Intravenous Administration in Rabbits

    PubMed Central

    Kim, Eunyoung; Kang, Wonku

    2013-01-01

    The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of 0.36 ± 0.05 h. Clearance and volume of distribution were 1.8 ± 0.6 L/h/kg and 0.58 ± 0.32 L/kg, respectively. The area under the plasma concentration-time curves (AUC) was 59.7 ± 18.2 μg·hr/ml, and urinary excretion up to 12 hr was ~7.7% of the dose. Plasma uridine reached a peak of 25.8 ± 4.1 μg/ml at 2.3 ± 0.8 hr after oral administration. The AUC was 79.0 ± 13.9 μg·hr/ml, representing ~29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine. PMID:24009876

  19. Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration.

    PubMed

    Golasik, Magdalena; Herman, Małgorzata; Olbert, Magdalena; Librowski, Tadeusz; Szklarzewicz, Janusz; Piekoszewski, Wojciech

    2016-04-15

    Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients. PMID:26892718

  20. Nanocarriers and the delivered drug: effect interference due to intravenous administration.

    PubMed

    Vlasova, Maria A; Rytkönen, Jussi; Riikonen, Joakim; Tarasova, Olga S; Mönkäre, Juha; Kovalainen, Miia; Närvänen, Ale; Salonen, Jarno; Herzig, Karl-Heinz; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-10-15

    Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself. PMID:24964293

  1. Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration.

    PubMed

    Sundlof, S F; Whitlock, T W

    1992-09-01

    Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one-compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats. PMID:1433492

  2. Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses.

    PubMed

    Chiavaccini, L; Claude, A K; Lee, J H; Ross, M K; Meyer, R E; Langston, V C

    2015-08-01

    The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half-life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady-state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half-lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses. PMID:25484250

  3. Pharmacokinetics of marbofloxacin in rabbit after intravenous, intramuscular, and subcutaneous administration.

    PubMed

    Marín, P; Alamo, L F; Escudero, E; Fernández-Varón, E; Hernandis, V; Cárceles, C M

    2013-06-01

    The disposition kinetics of marbofloxacin, a fluoroquinolone antibiotic, after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration was determined in rabbits at a single dose of 2 mg/kg. Plasma concentrations of marbofloxacin were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and non-compartmental pharmacokinetic methods. Steady-state volume of distribution (V(ss)) and clearance (Cl) of marbofloxacin after i.v. administration were 1.99±0.27 L/kg and 0.42±0.04 L/h kg, respectively. Following i.m. and s.c. administration marbofloxacin achieved maximum plasma concentrations of 2.04±0.32 and 1.64±0.15 mg/L at 0.33±0.16 and 0.50±0.18 h, respectively. The absolute bioavailabilities after i.m. and s.c. routes were 123.30±17.64% and 114.81±12.11%, respectively. From these data (kinetic parameters and absence of adverse reactions) marbofloxacin is likely to be effective in rabbits. PMID:23434066

  4. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. PMID:26102179

  5. Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles.

    PubMed

    Conceição, Mariana; Mendonça, Liliana; Nóbrega, Clévio; Gomes, Célia; Costa, Pedro; Hirai, Hirokazu; Moreira, João Nuno; Lima, Maria C; Manjunath, N; de Almeida, Luís Pereira

    2016-03-01

    In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs). To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled "Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype" (Conceição et al., in press) [1]. PMID:26958628

  6. Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

    PubMed Central

    Conceição, Mariana; Mendonça, Liliana; Nóbrega, Clévio; Gomes, Célia; Costa, Pedro; Hirai, Hirokazu; Moreira, João Nuno; Lima, Maria C.; Manjunath, N.; de Almeida, Luís Pereira

    2016-01-01

    In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs). To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled “Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado–Joseph disease neurological phenotype” (Conceição et al., in press) [1]. PMID:26958628

  7. Intravenous iron administration and hypophosphatemia in clinical practice.

    PubMed

    Hardy, S; Vandemergel, X

    2015-01-01

    Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32-0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed. PMID:26000018

  8. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

    PubMed Central

    Hardy, S.; Vandemergel, X.

    2015-01-01

    Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed. PMID:26000018

  9. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock

    PubMed Central

    Strandberg, G; Larsson, A; Lipcsey, M; Michalek, J; Eriksson, M

    2015-01-01

    Background We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock. Methods In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations. Results For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71–1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62–1.19). Conclusions In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult. PMID:25557933

  10. Pharmacokinetics and Bioavailability of a Therapeutic Enzyme (Idursulfase) in Cynomolgus Monkeys after Intrathecal and Intravenous Administration

    PubMed Central

    Xie, Hongsheng; Chung, Jou-Ku; Mascelli, Mary Ann; McCauley, Thomas G.

    2015-01-01

    Intravenous enzyme replacement therapy with iduronate-2-sulfatase is an approved treatment for Hunter syndrome, however, conventional intravenous delivery cannot treat the neurologic manifestations of the disease due to its limited central nervous system penetration. Intrathecal administration of iduronate-2-sulfatase for delivery to the central nervous system is currently under investigation. The objective of this study was to evaluate the pharmacokinetics of idursulfase in the central nervous system of cynomolgus monkeys (Macaca fasicularis) after intravenous and intrathecal administration. Twenty-seven monkeys, treatment-naïve to enzyme replacement therapy, were placed into 4 groups according to body weight: Group 1 was administered 0.5 mg/kg idursulfase intravenously, Groups 2–4 were administered an intrathecal formulation (1-, 10-, and 30-mg doses). Blood samples and cerebrospinal fluid (sampled at the cisterna magna or lumbar level) were collected at the same time points for 72 hours post dosing. Following intravenous administration, a high maximum serum concentration and rapid distribution of iduronate-2-sulfatase out of the central compartment were observed (elimination half-life: 4.3 hours). Iduronate-2-sulfatase exposure in the cerebrospinal fluid was limited, suggesting intravenous administration provided minimal penetration of the blood–brain barrier. Following intrathecal administration, a high maximum observed concentration was immediately noted and elimination half-life ranged between 7.8–10 hours and 5.9–6.7 hours (cisterna magna and lumbar sampling, respectively). Cerebrospinal fluid pharmacokinetic profiles at different doses of iduronate-2-sulfatase were similar and the dose/exposure relationship was proportional. After intrathecal administration, movement of iduronate-2-sulfatase from cerebrospinal fluid to serum was observed (systemic bioavailability was 40–83%). The clear penetration of iduronate-2-sulfatase into the cerebrospinal

  11. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

    PubMed Central

    Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

    2016-01-01

    Purpose Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results Both intravenously and EP-administered neostigmine (0.2–66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. PMID:27274203

  12. Real-Time Scintigraphic Assessment of Intravenous Radium-223 Administration for Quality Control

    PubMed Central

    Wright, Chadwick L.; Monk, J. Paul; Murrey, Douglas A.; Hall, Nathan C.

    2015-01-01

    Radium-223 (223Ra) dichloride is an approved intravenous radiotherapy for patients with osseous metastases from castration-resistant prostate cancer (CRPC). In addition to the therapeutic alpha radiation, there is additional 223Ra radiation generated which produces photons that can be imaged with conventional gamma cameras. No studies have evaluated real-time and quality imaging during intravenous 223Ra administration to verify systemic circulation and exclude 223Ra extravasation at the injection site. A retrospective review was performed for fifteen 223Ra administrations for CRPC patients which were imaged using a large field of view portable gamma camera (LFOVPGC) for the purposes of quality control and patient safety. Dynamic imaging of the chest was performed before, during, and after the 223Ra administration to verify systemic circulation, per institutional clinical protocol. Before and after 223Ra administration, a static image was obtained of the intravenous access site. Dynamic imaging of the chest confirmed systemic administration early during the 1-minute injection period for all patients. There were no cases of focal 223Ra extravasation at the site of intravenous access. These results verify that systemic 223Ra administrations can be quantified with real-time imaging using an LFOVPGC. This simple approach can confirm and quantify systemic circulation of 223Ra early during injection and exclude focal extravasation for the purposes of quality control. PMID:25789312

  13. Pharmacokinetics and plasma concentrations of acetylsalicylic acid after intravenous, rectal, and intragastric administration to horses.

    PubMed

    Broome, Ted A; Brown, Murray P; Gronwall, Ronald R; Casey, Matthew F; Meritt, Kelly A

    2003-10-01

    Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (+/- the standard error of the mean) was 1.32 +/- 0.09 h(-1), the mean elimination half-life was 0.53 +/- 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 +/- 98 microg x min/mL, the plasma clearance was 472 +/- 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 +/- 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 +/- 0.80 microg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 +/- 5.46 microg/mL at 2 h, then decreased to 1.92 +/- 0.25 microg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 +/- 94.55 microg x min/mL and the bioavailability was 0.17 +/- 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 +/- 0.10 microg/mL at 0.67 h, then declined to 0.37 +/- 0.37 microg/mL by 36 h; the plasma concentration of SA peaked at 23.90 +/- 4.94 microg/mL at 4 h and decreased to 0.85 +/- 0.31 microg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 +/- 24.90 microg x min/mL and the bioavailability was 0.059 +/- 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate. PMID:14620867

  14. Maternal Intravenous Administration of Azithromycin Results in Significant Fetal Uptake in a Sheep Model of Second Trimester Pregnancy

    PubMed Central

    Miura, Yuichiro; Payne, Matthew S.; Jobe, Alan H.; Kallapur, Suhas G.; Saito, Masatoshi; Stock, Sarah J.; Spiller, O. Brad; Ireland, Demelza J.; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A.; Newnham, John P.

    2014-01-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  15. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy.

    PubMed

    Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Spiller, O Brad; Ireland, Demelza J; Yaegashi, Nobuo; Clarke, Michael; Hahne, Dorothee; Rodger, Jennifer; Keelan, Jeffrey A; Newnham, John P

    2014-11-01

    Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks of gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation age-approriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intra-amniotic AZ dose or repeated maternal intravenous (i.v.) AZ doses would safely yield therapeutic levels of AZ in an 80-day-gestation (term is 150 days) ovine fetus. Fifty sheep carrying single pregnancies at 80 days gestation were randomized to receive either: (i) a single intra-amniotic AZ administration or (ii) maternal intravenous AZ administration every 12 h. Amniotic fluid, maternal plasma, and fetal AZ concentrations were determined over a 5-day treatment regimen. Markers of liver injury and amniotic fluid inflammation were measured to assess fetal injury in response to drug exposure. A single intra-amniotic administration yielded significant AZ accumulation in the amniotic fluid and fetal lung. In contrast, repeated maternal intravenous administrations achieved high levels of AZ accumulation in the fetal lung and liver and a statistically significant increase in the fetal plasma drug concentration at 120 h. There was no evidence of fetal injury in response to drug exposure. These data suggest that (i) repeated maternal i.v. AZ dosing yields substantial fetal tissue uptake, although fetal plasma drug levels remain low; (ii) transfer of AZ from the amniotic fluid is less than transplacental transfer; and (iii) exposure to high concentrations of AZ did not elicit overt changes in fetal white blood cell counts, amniotic fluid monocyte chemoattractant protein 1 concentrations, or hepatotoxicity, all consistent with an absence of fetal injury. PMID:25155606

  16. Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers.

    PubMed Central

    Flor, S C; Rogge, M C; Chow, A T

    1993-01-01

    The bioequivalence of oral and intravenous ofloxacin was investigated after the administration of multiple doses of 400 mg every 12 h to 20 healthy male volunteers in a randomized, crossover, open-label study. Ofloxacin concentrations in plasma were evaluated after 4 days of oral or intravenous (1-h infusion) dosing with a 3-day wash-out period between regimens. As expected, delivery to the systemic circulation took slightly longer after the oral dosing (time to maximum concentration of drug in serum of 1.7 h) relative to the 1-h intravenous infusion, but the systemic availabilities of ofloxacin by the two routes of administration were equivalent (area under the concentration-time curve from 0 to 12 h ratio of 95%). Since previous studies have not demonstrated any change in the bioavailability of ofloxacin in infectious disease patients, this study supports the interchangeability of these dosing regimens. PMID:8363378

  17. Medroxyprogesterone acetate plasma pharmacokinetics after intravenous administration in rabbits.

    PubMed

    Pannuti, F; Camaggi, C M; Strocchi, E; Comparsi, R

    1987-01-01

    Medroxyprogesterone acetate (MAP) plasma pharmacokinetics was followed up in a total of 30 New Zealand rabbits after i.v. administration (0.1, 0.5, and 1.0 mg/kg) of either an aqueous suspension or a homogeneous solution of the drug in dimethylsulphoxide (DMSO). A well-defined triphasic decay of MAP plasma levels was noticeable in the animals treated with DMSO solutions. A delayed concentration peak was often present when aqueous suspensions were used, so if is not feasible to fit the experiment with simple polyexponential equations. Model-independent pharmacokinetic analysis (statistical moment theory) revealed a significant dependence of plasma clearance and mean residence time on the dose administered in both conditions. PMID:2954713

  18. INTRAVENOUS MEDICATION ADMINISTRATION ERRORS AND THEIR CAUSES IN CARDIAC CRITICAL CARE UNITS IN IRAN

    PubMed Central

    Bagheri-Nesami, Masoumeh; Esmaeili, Ravanbakhsh; Tajari, Mojdeh

    2015-01-01

    Background and Objectives: The dangerous events caused by medication errors are one of the main challenges faced in critical care units. The present study was conducted to determine the frequency of intravenous medication administration errors and their causes in cardiac critical care units in Iran. Materials and Methods: The present descriptive study was conducted in the critical care units (CCUs and cardiac surgery intensive care units) of 12 teaching hospitals. Of the total of 240 nurses working in these departments, 190 participated in the present study. The data collection tools used in this study included the “nurses’ demographic data questionnaire”, the “patients’ medical and demographic data questionnaire” and the “nurses’ self-reporting questionnaire about the frequency of intravenous medication administration errors and their causes”. The data obtained were analyzed in SPSS-20 using descriptive statistics such as the absolute and relative frequency. Findings: During the 2 months in which this study was being conducted, 2542 patients were admitted to these departments and 20240 doses of intravenous medications were administered to these patients. The nurses reported 262 intravenous medication administration errors. The most common intravenous medication error pertained to administering the wrong medication (n=71 and 27.1%). As for the causes of intravenous medication administration errors, 51.5% of the errors were associated with work conditions, 24% with packaging, 13.4% with communication, 9.9% with transcription and 1.2% with pharmacies. Discussion and Conclusion: According to the results, strategies are recommended to be adopted for reducing or limiting medication errors, such as building a stronger pharmacology knowledge base in nurses and nursing students, improving work conditions and improving communication between the nurses and physicians. PMID:26889108

  19. Pharmacokinetics of cyclophosphamide and alkylating activity in man after intravenous and oral administration

    PubMed Central

    Juma, F. D.; Rogers, H. J.; Trounce, J. R.

    1979-01-01

    1 Plasma cyclophosphamide levels were estimated by gas-chromatography in seven patients following intravenous and oral cyclophosphamide administration. Plasma alkylating activity was determined by the nitrobenzyl pyridine (NBP) reaction. 2 The plasma T½ after intravenous administration ranged from 5.97 to 12.37 h but after oral administration was shorter, 1.32-6.8 h. The mean total body clearance was 66.6 ml kg-1 h-1 after intravenous dosing and 93.1 ml kg-1 h-1 following oral dosing. Vdβ was 0.71 (0.10 s.d.) 1 kg-1 suggesting that cyclophosphamide is distributed largely in body water. 3 The mean hepatic extraction ratio was 0.25, indicating a modest first pass metabolism. The metabolic clearance was 3.72 1 kg-1 and the intrinsic hepatic clearance 5.17 1 kg-1. 4 The mean renal clearance was 4.8 ml kg-1 h-1 with 6.5% of the administered dose excreted unchanged in the urine suggesting tubular reabsorption of cyclophosphamide. 5 The mean T½ of plasma alkylating activity was 8.82 h, there being no significant difference following oral and intravenous administration. On average, 3.5 times the alkylating activity was produced by an oral dose of cyclophosphamide as compared to an intravenous dose. It is possible that this may reflect production of a different pattern of alkylating metabolites following cyclophosphamide administration by different routes. The clinical significance of these observations is unknown. PMID:497087

  20. Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine hydrochloride in rats after intranasal and intravenous administration.

    PubMed

    Wang, Qiao; Tang, Zhan; Zhang, Wanggang

    2013-10-01

    The aim of this work was to investigate the pharmacokinetics of ligustrazine hydrochloride (LZH) in plasma, cerebrospinal fluid (CSF) and cerebral cortex after intranasal (10 mg/kg) or intravenous administration (10 mg/kg) in male Sprague-Dawley rats. Plasma, CSF and cerebral cortex microdialysates were collected at timed intervals for the measurement of LZH by a quick and sensitive HPLC-UV method. LZH entered the brain quickly following both routes of administration. No significant difference was observed between the AUCCSF or cortex /AUCplasma ratio of LZH after intranasal administration (38.4%, 17.4%) and that after intravenous injection (45.9%, 19.9%). The drug targeting index (DTI) was 0.85 and 0.91 in the CSF and cortex, respectively. In conclusion, LZH is rapidly absorbed into the systemic circulation following intranasal administration. There is no direct pathway for LZH transport from the nasal cavity to the brain. The rapidity and magnitude of LZH penetration into the brain indicate that intranasal administration of this agent is a promising alternative to intravenous administration. PMID:23868712

  1. Evaluation of lipid peroxidation activity at intravenous administration of gold nanorods in rats with simulated diabetes and transplanted liver cancer

    NASA Astrophysics Data System (ADS)

    Bucharskaya, Alla B.; Dikht, Natalia I.; Afanasyeva, Galina A.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Zaraeva, Nadezhda V.; Khlebtsov, Nikolai G.; Khlebtsov, Boris N.

    2014-01-01

    In the experiment the white outbred rats with transplanted liver cancer (cholangiocarcinoma line PC-1) and simulated alloxan diabetes were treated by single intravenous injection of gold nanorods. State of lipid peroxidation was evaluated by the following parameters: the malondialdehyde, lipid hydroperoxide, the average weght molecules in the serum of animals by conventional spectrophotometric methods study using a spectrofluorometer RF-5301 PC (Shimadzu, Japan). In both experimental groups of animals the significant increasing of levels of lipid peroxidation products was noted compared with control group. After intravenous administration of nanoparticles in the group of animals with alloxan diabetes the activation of a free radical oxidation was not observed, in group with transplanted liver cancer the increasing of levels of lipid hydroperoxide, malondialdehyde was established.

  2. Does Intravenous Administration of Recombinant Tissue Plasminogen Activator for Ischemic Stroke can Cause Inferior Myocardial Infarction?

    PubMed Central

    Almasi, Mostafa; Razmeh, Saeed; Habibi, Amir Hassan; Rezaee, Amir Hassan

    2016-01-01

    Recombinant tissue plasminogen activator (rTPA) is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI) is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved. PMID:27441068

  3. Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation.

    PubMed

    Corey, A E; Agnew, J R; Valentine, S N; Nesbitt, J D; Wagner, D L; Powell, J H; Thompson, G A

    1999-12-01

    Azimilide dihydrochloride (NE-10064) is a novel class III anti-arrhythmic agent that blocks both the slowly and rapidly acting components of the delayed rectifier potassium current of human atrial and ventricular myocytes. In clinical studies, azimilide reduced the frequency of symptomatic episodes of atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. This study was conducted to characterize azimilide pharmacokinetics following single-dose administration of a 1 mg/kg intravenous infusion (18 min), 2 mg/kg oral solution, and a 150 mg orally administered capsule. This was a three-period, randomized, crossover study in 27 healthy, drug-free (including caffeine and alcohol), non-smoking male volunteers (mean [SD]; age, 25.9 [1.0] years; weight 74.3 [0.7] kg; 23 Caucasians and 4 Hispanics). Blood and urine samples were collected for 27 days and analyzed for azimilide using HPLC with UV detection. Subjects were monitored for adverse events and abnormalities in clinical laboratory tests, vital signs, and electrocardiography (including Holter monitoring). Mean (%CV) azimilide parameters were total clearance = 0.143 L/h/kg (38%), renal clearance = 0.014 L/h/kg (35%), steady-state volume of distribution = 13.2 L/kg (23%), and terminal exponential half-life = 78.8 h (44%). Similar parameter estimates were obtained following oral administration. Both the oral solution and capsule formulations were completely absorbed. In addition, the rate (Cmax) and extent of absorption (AUC) following oral administration of the capsule dosage form were bioequivalent to the oral solution with means for times of maximum blood concentration of 7.08 and 7.18 hours for the oral solution and capsule, respectively. Azimilide dihydrochloride was generally well tolerated in all subjects. PMID:10586393

  4. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    PubMed Central

    Soliman, Ahmed

    2014-01-01

    The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV) and oral (PO) dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β)) and mean residence time (MRT) were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot) in renal damaged ducks (0.20 L kg−1 h−1) was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1). Following PO administration, the peak serum concentration (Cmax) was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax) of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el)) at a significant slower rate (3.94 h) in renal damaged than in healthy ducks (2.89 h). The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks. PMID:24707439

  5. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    PubMed Central

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  6. Pharmacokinetics of A40926 in rats after single intravenous and subcutaneous doses.

    PubMed Central

    Bernareggi, A; Danese, A; Cavenaghi, L

    1988-01-01

    A40926 is a new glycopeptide antibiotic with unique activity against Neisseria gonorrhoeae and high and prolonged levels in mouse blood (B. P. Goldstein, E. Selva, L. Gastaldo, M. Berti, R. Pallanza, F. Ripamonti, P. Ferrari, M. Denaro, V. Arioli, and G. Cassani, Antimicrob. Agents Chemother., 31:1961-1966, 1987). We studied the pharmacokinetics of A40926 in rats after single intravenous and subcutaneous 10-mg/kg (body weight) doses. Concentrations in plasma and urine were determined by microbiological assay. After intravenous administration, high concentrations of A40926, ranging from 132 mg/liter at 3 min to 0.7 mg/liter at 96 h, were found in plasma. Concentrations declined with a three-exponential decay correlated with a prolonged, biphasic distribution and a slow elimination (terminal half-life, 61.22 h). After completion of the distribution, the compound was widely distributed to the extravascular space. The rate-limiting step in the elimination of A40926 from the body appears to be the slow return from the deep compartment into the central one. A40926 was rapidly absorbed from the injection site after subcutaneous administration, and its availability was close to 90%. The percentage of the dose excreted in urine in 120 h was 35.9%. PMID:3364946

  7. Plasma disposition of enrofloxacin following intravenous and intramuscular administration in donkeys.

    PubMed

    Sekkin, S; Gokbulut, C; Kum, C; Karademir, U

    2012-11-01

    This study was designed to investigate the plasma disposition and systemic availability of enrofloxacin (ENR) following intramuscular and intravenous administrations. Six donkeys (Equus asinus) were used in this study. The animals were allocated into two groups (intramuscular and intravenous groups). After a 2-week washout period, the experiment was repeated with the groups reversed according to a two-phase crossover design. In phase I, group I received intravenously the commercially available injectable solution of ENR at the dose of 5 mg/kg and group II received intramuscularly the same ENR formulation at the same dose rate. Blood samples were collected 1 hour prior to drug administration and various times between 5 minutes and 48 hours post-treatments. The samples were analysed by high performance liquid chromatography with fluorescence detector. The half-life and mean residence time of ENR (12.08 hours and 17.85 hours) after intramuscular route were significantly longer compared with intravenous administration (9.54 hours and 7.46 hours, respectively) and these were associated with a flip-flop phenomenon. A marked proportion of ENR (20-21 per cent) was metabolised to ciprofloxacin (CPR) following both administration routes and the half-life of CPR paralleled that of the parent drug after intramuscular administration. Mean absorption time was relatively long (10.39 hours), and the bioavailability of ENR was 76.56 per cent after intramuscular route in the donkeys. The plasma concentration is lower after intramuscular administration at a dose rate of 5 mg/kg, and may need a higher dose to provide sufficient plasma concentration in donkeys compared with horses. PMID:23065257

  8. Single dose intravenous methyl prednisolone versus oral prednisolone in Bell's palsy: A randomized controlled trial

    PubMed Central

    Giri, Prithvi; Garg, Ravindra Kumar; Singh, Maneesh Kumar; Verma, Rajesh; Malhotra, Hardeep Singh; Sharma, Praveen Kumar

    2015-01-01

    Objectives: Corticosteroids have been used in the treatment of Bell's palsy and several other postinfectious neurological conditions. We hypothesized that administration of a single dose of intravenous (IV) methylprednisolone might be an effective alternative to oral prednisolone. Materials and Methods: In this open label, randomized trial, patients with acute Bell's palsy were randomized into two groups. One group received single dose (500 mg) of IV methylprednisolone while the other group received 10 days of oral prednisone. Outcome was assessed at 1 and 3 months with House–Brackmann scale. Results: At 3 months, 93 (79.48%) patients had completely recovered. IV methylprednisolone and oral prednisolone groups had similar recovery rates (80% vs. 78.33%, P > 0.05). Patients with Grade 2 and 3 recovered completely. In patients with Grade 6, the recovery rate was 20%. A better outcome was observed if corticosteroids were administered within 3 days of onset of palsy. Conclusion: Intravenous methylprednisolone and oral prednisolone showed equivalent benefit in patients with acute Bell's palsy. PMID:25878371

  9. Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate.

    PubMed

    Duconge, Jorge; Miranda-Massari, Jorge R; Gonzalez, Michael J; Jackson, James A; Warnock, William; Riordan, Neil H

    2008-03-01

    There is a strong advocacy movement for large doses of vitamin C. Some authors argue that the biological half-life for vitamin C at high plasma levels is about 30 minutes, but these reports are the subject of some controversy. NIH researchers established the current RDA based upon tests conducted 12 hours (24 half lives) after consumption. The dynamic flow model refutes the current low-dose recommendations for dietary intakes and links Pauling's mega-dose suggestions with other reported effects of massive doses of ascorbate for the treatment of disease. Although, a couple of controlled clinical studies conducted at The Mayo Clinic did not support a significant benefit for terminal cancer patients after 10 grams of once-a-day oral vitamin C, other clinical trials have demonstrated that ascorbate may indeed be effective against tumors when administered intravenously. Recent studies confirmed that plasma vitamin C concentrations vary substantially with the route of administration. Only by intravenous administration, the necessary ascorbate levels to kill cancer cells are reached in both plasma and urine. Because the efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated. One limitation of current studies is that pharmacokinetic data at high intravenous doses of vitamin C are sparse, particularly in cancer patients. This fact needs prompt attention to understand the significance of intravenous vitamin C administration. This review describes the current state-of-the-art in oral and intravenous vitamin C pharmacokinetics. In addition, the governmental recommendations of dose and frequency of vitamin C intake will also be addressed. PMID:18450228

  10. Acute hemodynamic effects and blood pool kinetics of polystyrene microspheres following intravenous administration

    SciTech Connect

    Slack, J.D.; Kanke, M.; Simmons, G.H.; DeLuca, P.P.

    1981-06-01

    The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 micrometer) were administered. The 7.4- and 11.6-micrometer diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administrations of the 7.4- and 11.6-micrometer diameter microspheres in doses as high as 3.0 X 10(9) and 6.1 X 10(8) respectively (total cross-sectional area of 1.3 X 10(11) and 6.4 X 10(10) micrometer2, respectively). Intravenous administration of 3.4-micrometer diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as slow as 1.0 X 10(10) (cross-sectional area of 9.1 X 10(10) micrometer2). These differences in acute hemodynamic effect from the 7.4- and 11.6-micrometer diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-micrometer diameter microspheres, which readily pass through the lungs to the spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 . 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 10(3) spheres/g of blood were present in the circulation for greater than 1 hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.

  11. Understanding the causes of intravenous medication administration errors in hospitals: a qualitative critical incident study

    PubMed Central

    Keers, Richard N; Williams, Steven D; Cooke, Jonathan; Ashcroft, Darren M

    2015-01-01

    Objectives To investigate the underlying causes of intravenous medication administration errors (MAEs) in National Health Service (NHS) hospitals. Setting Two NHS teaching hospitals in the North West of England. Participants Twenty nurses working in a range of inpatient clinical environments were identified and recruited using purposive sampling at each study site. Primary outcome measures Semistructured interviews were conducted with nurse participants using the critical incident technique, where they were asked to discuss perceived causes of intravenous MAEs that they had been directly involved with. Transcribed interviews were analysed using the Framework approach and emerging themes were categorised according to Reason's model of accident causation. Results In total, 21 intravenous MAEs were discussed containing 23 individual active failures which included slips and lapses (n=11), mistakes (n=8) and deliberate violations of policy (n=4). Each active failure was associated with a range of error and violation provoking conditions. The working environment was implicated when nurses lacked healthcare team support and/or were exposed to a perceived increased workload during ward rounds, shift changes or emergencies. Nurses frequently reported that the quality of intravenous dose-checking activities was compromised due to high perceived workload and working relationships. Nurses described using approaches such as subconscious functioning and prioritising to manage their duties, which at times contributed to errors. Conclusions Complex interactions between active and latent failures can lead to intravenous MAEs in hospitals. Future interventions may need to be multimodal in design in order to mitigate these risks and reduce the burden of intravenous MAEs. PMID:25770226

  12. The dangers of trying to make ends meet: accidental intravenous administration of enteral feed.

    PubMed

    Ramsay, S J; Gomersall, C D; Joynt, G M

    2003-06-01

    We report a case of inadvertent intravenous administration of enteral feed, a very rare but potentially life-threatening complication of enteral feeding. Bacterial contamination of feed results in a severe septic response that requires broad-spectrum antibiotic cover and aggressive organ support. The failure of measures aimed at prevention of this complication must be investigated, and practice changed to ensure that further incidents are avoided. PMID:12879682

  13. Single dose intravenous dexmedetomidine prolongs spinal anesthesia with hyperbaric bupivacaine

    PubMed Central

    Kubre, Jyotsna; Sethi, Ashish; Mahobia, Mamta; Bindal, Deeksha; Narang, Neeraj; Saxena, Anudeep

    2016-01-01

    Background and Introduction: Spinal block, a known technique to obtain anaesthesia for infraumblical surgeries. Now physician have advantage of using adjuvant to prolong the effect of intrathecal block, which can be given either intravenously or intrathecally, dexmedetomidine is one of them. We studied effect of intravenous dexmedetomidine for prolongation of duration of intrathecal block of 0.5% bupivacaine block. Objective: To evaluate the effect of intravenous dexmedetomidine on sensory regression, hemodynamic profile, level of sedation and postoperative analgesia. Methodology: 60 patients of ASA grade I and II posted for elective infraumblical surgeries were included in the study and randomly allocated into two groups. Group D recieved intrathecal 0.5% bupivacaine heavy, followed by infusion of intravenous dexmedetomidine 0.5mic/kg over 10 min, patients in group C received intrathecal 0.5% bupivacaine heavy 3ml followed by infusion of same volume of normal saline as placebo. Results: Two segment regression of sensory block was achieved at 139.0 ± 13.797 in group D whereas in group C it was only 96.67 ± 7.649min, the total duration of analgesia achieved in both study groups was 234.67 ± 7.649min and 164.17 ± 6.170min respectively in group D and group C. The time at which first analgesic was given to the patients when VAS >3 achieved that is in group D at 234.67 ± 7.649min and in group C at 164.17 ± 6.170min. Inj diclofenac sodium 75mg intramuscular was used as rescue analgesic. PMID:27212760

  14. Systemic gene delivery following intravenous administration of AAV9 to fetal and neonatal mice and late-gestation nonhuman primates.

    PubMed

    Mattar, Citra N; Wong, Andrew M S; Hoefer, Klemens; Alonso-Ferrero, Maria E; Buckley, Suzanne M K; Howe, Steven J; Cooper, Jonathan D; Waddington, Simon N; Chan, Jerry K Y; Rahim, Ahad A

    2015-09-01

    Several acute monogenic diseases affect multiple body systems, causing death in childhood. The development of novel therapies for such conditions is challenging. However, improvements in gene delivery technology mean that gene therapy has the potential to treat such disorders. We evaluated the ability of the AAV9 vector to mediate systemic gene delivery after intravenous administration to perinatal mice and late-gestation nonhuman primates (NHPs). Titer-matched single-stranded (ss) and self-complementary (sc) AAV9 carrying the green fluorescent protein (GFP) reporter gene were intravenously administered to fetal and neonatal mice, with noninjected age-matched mice used as the control. Extensive GFP expression was observed in organs throughout the body, with the epithelial and muscle cells being particularly well transduced. ssAAV9 carrying the WPRE sequence mediated significantly more gene expression than its sc counterpart, which lacked the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) sequence. To examine a realistic scale-up to larger models or potentially patients for such an approach, AAV9 was intravenously administered to late-gestation NHPs by using a clinically relevant protocol. Widespread systemic gene expression was measured throughout the body, with cellular tropisms similar to those observed in the mouse studies and no observable adverse events. This study confirms that AAV9 can safely mediate systemic gene delivery in small and large animal models and supports its potential use in clinical systemic gene therapy protocols. PMID:26062602

  15. Medication Errors Involving the Intravenous Administration Route: Characteristics of Voluntarily Reported Medication Errors.

    PubMed

    Wolf, Zane Robinson

    2016-01-01

    Characteristics of medication errors involving the intravenous (IV) route of administration were analyzed in reports from 1995 to 2013. This was accomplished through a voluntary medication error reporting program. A retrospective case study design analyzed reports by practitioners or consumers on IV-associated medication errors (N = 975) affecting patients. Patterns in error accounts reflected cultural changes in health care organizations. Equipment, labeling, incorrect route of administration, types of errors, patient outcomes, and causal agents represented major codes. Results point to health care provider and consumer knowledge, the need for ongoing education of nursing staff, and interdisciplinary strategies for preventing IV-associated medication errors. PMID:27379682

  16. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

    SciTech Connect

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

    1986-07-01

    Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing.

  17. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  18. Serum Concentration and Drug Effect After Intravenous and Rectal Administration of Diazepam

    PubMed Central

    Lundgren, Stefan

    1987-01-01

    In a randomized crossover study on sedation in outpatient oral surgery, the relation between the serum profile and the drug effect profile for intravenously (i.v.) and rectally administered diazepam was studied. Both sedation methods were found to be equally efficient at a mean dose of 0.25 mg/kg (range, 0.14—0.45) for i.v. administration, and 0.53 mg/kg (range, 0.50—0.58) for rectal administration. Both the serum concentration and the effect reached their mean peaks at the same time; however, this was 15 min later after rectal sedation than after i.v. sedation. Intravenous administration yielded a significantly higher serum concentration of diazepam at the clinical endpoint than did rectal administration, but the mean effect levels at the clinical endpoint were equal for both sedation methods. No linear correlation between log-serum concentration and the patient's estimation of effect was found. PMID:3481512

  19. Biodistribution of gold nanoparticles synthesized by γ-irradiation after intravenous administration in mice

    NASA Astrophysics Data System (ADS)

    Luan Le, Quang; Phuong Linh Do, Thi; Phuong Uyen Nguyen, Huynh; Phu Dang, Van; Hien Nguyen, Quoc

    2014-06-01

    In the present research work we evaluate the in vivo distribution of gold nanoparticles (AuNPs) at different time durations after intravenous administration in mice. AuNPs with size of about 20 nm and concentration of 1 mM were synthesized by gamma irradiation method using 0.5% alginate as a stabilizer. AuNPs were characterized by UV-Vis spectrum and transmission electron microscope (TEM) image. The as-synthesized AuNPs solution was centrifuged to concentrate to 2 mg AuNPs/1 ml solution. Intravenous administration of AuNPs in mice was done at the tail with 1 mg AuNPs (0.5 ml). After 1, 3, 6 and 12 h of injection, blood was collected, mice were sacrificed and various tissues/organs were removed. The blood haematology and serum clinical chemistry indexes of mice intravenously injected with AuNPs were not significantly different compared to those of the control ones. In addition, gold content in the samples was quantitatively determined by k0-neutron activation analysis (k0-NAA) at nuclear research reactor, Da Lat Vietnam. Results showed that after 1 h of administration, AuNPs were mainly accumulated in blood (41.56%), in liver (51.60.%), in lung (6.16%) and in kidney (0.53%). After that the content of AuNPs in blood was decreased to nearly normal at 6 h while the content of AuNPs in liver, lung and kidney was accumulatively increased. After 6 h of administration AuNPs were mainly accumulated in organs like liver (76.33%), lung (11.86%) and kidney (2.23%). Thus, the obtained results are practically useful for using AuNPs as x-ray contrast agent, especially for blood and liver.

  20. Disposition, metabolism and mass balance of delafloxacin in healthy human volunteers following intravenous administration.

    PubMed

    McEwen, Andrew; Lawrence, Laura; Hoover, Randy; Stevens, Lloyd; Mair, Stuart; Ford, Gill; Williams, Dylan; Wood, Stuart

    2015-01-01

    1. The pharmacokinetics and disposition of delafloxacin was investigated following a single intravenous (300 mg, 100 µCi) dose to healthy male subjects. 2. Mean Cmax, AUC0-∞, Tmax and t1/2 values for delafloxacin were 8.98 µg/mL, 21.31 µg h/mL, 1 h and 2.35 h, respectively, after intravenous dosing. 3. Radioactivity was predominantly excreted via the kidney with 66% of the radioactive dose recovered in the urine. Approximately 29% of the radioactivity was recovered in the faeces, giving an overall mean recovery of 94% administered radioactivity. 4. The predominant circulating components were identified as delafloxacin and a direct glucuronide conjugate of delafloxacin. PMID:25986539

  1. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    PubMed

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease. PMID:27324760

  2. Pharmacokinetics of tramadol in horses after intravenous, intramuscular and oral administration.

    PubMed

    Shilo, Y; Britzi, M; Eytan, B; Lifschitz, T; Soback, S; Steinman, A

    2008-02-01

    Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were determined in the obtained plasma samples by use of an LC/MS/MS method and were used for pharmacokinetic calculations. Tramadol clearance, apparent volume of distribution at steady-state, mean residence time (MRT) and half-life after intravenous administration were 26+/-3 mL/min/kg, 2.17+/-0.52 L/kg, 83+/-10 min, and 82+/-10 min, respectively. The MRT and half-life after intramuscular administration were 155+/-23 and 92+/-14 min. The mean absorption time was 72+/-22 min and the bioavailability 111+/-39%. Tramadol was poorly absorbed after oral administration and only 3% of the administered dose was found in systemic circulation. The fate of the tramadol M1 metabolite was also investigated. M1 appeared to be a minor metabolite in horses, which could hardly be detected in plasma samples. The poor bioavailability after oral administration and the short half-life of tramadol may restrict its usefulness in clinical applications. PMID:18177320

  3. Intravenous vs intraperitoneal mesenchymal stem cells administration: What is the best route for treating experimental colitis?

    PubMed Central

    Gonçalves, Fabiany da Costa; Schneider, Natália; Pinto, Fernanda Otesbelgue; Meyer, Fabíola Schons; Visioli, Fernanda; Pfaffenseller, Bianca; Lopez, Patrícia Luciana da Costa; Passos, Eduardo Pandolfi; Cirne-Lima, Elizabeth Obino; Meurer, Luíse; Paz, Ana Helena

    2014-01-01

    AIM: To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis. METHODS: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 × 106 MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling assay. RESULTS: Intravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with

  4. [Imprecision of vancomycin prepared for intravenous administration at the bedside in a neonatal intensive care unit].

    PubMed

    Popescu, M; Vialet, R; Loundou, A; Peyron, F; Buès-Charbit, M

    2011-10-01

    In pediatric units, most of the intravenous medications are prepared by the attending nurse at the bedside that can be affected by an error margin, so can be imprecise. Despite the possible consequences of imprecise medications administration, published studies on the topic are scarce. The main objective of this study was to measure the difference between the prescribed vancomycine concentration and the actual concentration measured in the medication administered to the patient. The secondary objective was to determine which step in the preparation was linked to the difference in concentrations. It was a prospective study, setting in a pediatric and neonatal university hospital intensive care unit. Over a 3-month period, an aliquot from every preparation for continuous infusion of vancomycin, made at the bedside by a nurse, was collected and the modalities of the preparation noted. Vancomycin concentration was measured by high performance liquid chromatography. Sixty-four preparations, accounting for 24 patients (gestationnal age: 67 ± 75 weeks, weigh: 4.8 ± 6.5 kg) were included. Vancomycin concentrations ranged from 3.33 to 60.0mg/mL. Measured concentration were in mean 7% smaller than prescribed concentration (P<10(-3)), with a large confidence interval (75.8%-120.4% of the prescribed concentration). Imprecision the preparations was much higher than this admitted for manufactured preparation. We could not highlight any factor related to the difference in concentrations, but one third of the preparation did not respect all the ISO 7886 standards for syringes use. Bedside vancomycin preparations, like preparations for other molecules, are far more imprecise than industrial intravenous medications. Our results urge that all pediatric intravenous medications should be made only by manufacturers or pharmacists. However, it also urged clinical studies, in parallel to pharmacodynamic and pharmacokinetic studies, to make intravenous treatments as accurate as they

  5. Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

    PubMed Central

    Toombs, Christopher F; Insko, Michael A; Wintner, Edward A; Deckwerth, Thomas L; Usansky, Helen; Jamil, Khurram; Goldstein, Brahm; Cooreman, Michael; Szabo, Csaba

    2010-01-01

    INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005–0.20 mg kg−1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1–5 min following administration of IK-1001 at 0.10 mg kg−1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S. PMID:20565454

  6. Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep.

    PubMed

    Pérez, R; Palma, C; Drápela, C; Sepulveda, M; Espinoza, A; Peñailillo, A K

    2015-04-01

    Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS-induced acute-phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 μg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann-Whitney U-test. The mean values of AUC0-∞ in the endotoxaemic sheep (105.9 ± 14.3 μg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 μg·h/mL). The total mean plasma clearance (CLT ) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS-treated sheep. A significant increase (P < 0.05) in the terminal half-life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the

  7. The socio-economical impact of intravenous (IV) versus subcutaneous (SC) administration of trastuzumab: future prospectives.

    PubMed

    Papadmitriou, K; Trinh, X B; Altintas, S; Van Dam, P A; Huizing, M T; Tjalma, W A A

    2015-01-01

    Trastuzumab was the first targeted therapy for HER2 positive breast cancer. It has become the standard of care for HER2 positive metastatic breast cancer since 2000 and in the adjuvant setting since 2006. Adjuvant it is given for a year and in patients with metastatic disease until progression. The standard mode of administration is intravenous. Recently a subcutaneous form has become available. A phase III study showed that there is no difference between the intravenous and subcutaneous form in terms of safety and efficacy. The patient's preference however significantly favoured the subcutaneous form. It is estimated that the use of the SC form could contribute to a cost saving between 758 and 2576 euro per annual course. For Belgium alone this could mean an estimated saving of 1.4 to 4.6 million euros per year. The potential benefit of the SC administration for healthcare facilities could be further increased when applied in a LEAN working day-care chemotherapy unit. After reviewing the existing literature we suggest to further validate the potential financial impact of SC trastuzumab compared to the traditional IV form and to introduce a scientific proposal incorporating the benefits of this formulation in a LEAN working healthcare unit. PMID:26977267

  8. A novel strategy for encapsulating poorly soluble drug into nanostructured lipid carriers for intravenous administration.

    PubMed

    Zhao, Chunyan; Liu, Yan; Fan, Tingting; Zhou, Dan; Yang, Yang; Jin, Yun; Zhang, Zhirong; Huang, Yuan

    2012-01-01

    The present study aimed to formulate dexamethasone (DXM), a poorly soluble drug, into nanostructured lipid carriers (NLCs) for intravenous administration by employing a phospholipids complex. Initially, dexamethasone-phospholipids complex (DPC) was synthesized and characterized. Subsequently, DPC was entrapped into NLCs and the process was optimized using spherical symmetric design-surface response methodology. Then, the characteristics, in vitro release behavior and physical stability of the optimized DPC loaded NLCs (DPC-NLCs) were investigated. Comparison between DPC-NLCs and free DXM loaded NLCs was also conducted in the aspects of particle size, entrapment efficiency (EE), drug loading efficiency (DL), initial release and zeta potential. The results showed the optimized DPC-NLCs were prepared with an average size of 189.33 ± 0.58 nm, EE of 89.82 ± 1.64%, DL of 2.13 ± 0.13% and good physical stability for 30 days. In vitro release profile exhibited an initial burst release followed by a prolonged release. Compared with free DXM loaded NLCs, the EE and DL of DPC-NLCs were higher while the initial release was lower. These advantages of DPC-NLCs proved the phospholipids complex played an essential role in NLCs formulation and showed the potential for intravenous administration of poorly soluble drugs. PMID:21222507

  9. Pharmacokinetics of homoplantaginin in rats following intravenous, peritoneal injection and oral administration.

    PubMed

    Cong, Youquan; Wu, Song; Han, Jingjing; Chen, Jun; Liu, Hang; Sun, Qiwen; Wu, Yu; Fang, Yun

    2016-09-10

    The purpose of the present paper was to study the pharmacokinetic characteristics of homoplantaginin, a major active ingredient of Salvia plebeia R.Br. In this study, the effective partition coefficient, in situ absorption in rat intestinal segments and in vitro biotransformation of homoplantaginin by rat intestinal bacteria were determined. In addition, homoplantaginin was administered to rats by intravenous, peritoneal injection and oral administration. The concentrations of homoplantaginin and hispidulin, a metabolite of homoplantaginin, were determined by a validated highperformance liquid chromatographic (HPLC) assay. After intravenous, peritoneal injection, the concentration of hispidulin could not be determined. In contrast, after oral administration, hispidulin and homoplantaginin were simultaneous quantified, homoplantaginin was rapidly absorbed (Tmax=16.00±8.94min), reaching a mean Cmax between 0.77 and 1.27nmol/mL. The absolute oral bioavailability was calculated to be only 0.75%, and the area under curve (AUC) of hispidulin was about 5.4 times than that of homoplantaginin. The poor oral bioavailability may be attributed to the biotransformation of homoplantaginin by rat intestinal bacteria. PMID:27474945

  10. Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (IV) and intramuscular (IM) administration. Four healthy, opioid-naïve, socially-housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, post-administration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the IV study as compared to the IM study was 177 (159–189) minutes vs. 185 (174–214) minutes, respectively [median (range)]. In the IV study, concentration back extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the IM study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations greater than 0.10 ng/mL for over 24 h in the IV study and over 12 h in the IM study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study. PMID:24666428

  11. Dose-dependent pharmacokinetics and brain penetration of rufinamide following intravenous and oral administration to rats.

    PubMed

    Gáll, Zsolt; Vancea, Szende; Szilágyi, Tibor; Gáll, Orsolya; Kolcsár, Melinda

    2015-02-20

    Rufinamide is a third-generation antiepileptic drug, approved recently as an orphan drug for the treatment of Lennox-Gastaut syndrome. Although extensive research was conducted, its pharmacokinetics in rats was not described. This work addresses that area by describing in a rapid pharmacokinetic study the main pharmacokinetic properties of rufinamide at three different doses of 1 mg/kg body weight (bw), 5 mg/kg bw, and 20 mg/kg bw. Furthermore, total brain concentrations of the drug were determined in order to characterize its brain-to-plasma partition coefficient. Adult Wistar male rats, weighing 200-450 g, were administered rufinamide by intravenous and oral routes. Rufinamide concentrations from plasma samples and brain tissue homogenate were determined using a liquid chromatography-mass spectrometric method and pharmacokinetic parameters were calculated. The mean half-life was between 7 and 13 h, depending on route of administration--intravenously administered drug was eliminated faster than orally administered drug. Mean (S.E.M.) total plasma clearance was 84.01 ± 3.80 ml/h/kg for intravenous administration, while the apparent plasma clearance for oral administration was 95.52 ± 39.45 ml/h/kg. The mean (S.E.M.) maximum plasma concentration reached after oral administration of 1 mg/kg bw and 5 mg/kg bw was 0.89 ± 0.09 μg/ml and 3.188 ± 0.71 μg/ml, respectively. The median (range) time to reach maximum plasma concentration (t(max)) was 4 (2-8)h. Mean (S.E.M.) brain-to-plasma concentration ratio of rufinamide was 0.514 ± 0.036, consistent with the brain-to-plasma ratio calculated from the area under curves (AUC(0-t)) of 0.441 ± 0.047. No influence of dose, route of administration, or post-dosing time was observed on brain-to-plasma ratio. PMID:25530452

  12. Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats

    PubMed Central

    Miller, ML; Vaillancourt, BD; Wright, MJ; Aarde, SM; Vandewater, SA; Creehan, KM; Taffe, MA

    2011-01-01

    Background Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity. Methods Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1–14, 8–21 or 15–21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1–14, 8–21 or 15–28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel. Results METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions. Conclusions These data show METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer. PMID:21899959

  13. Changes of phylloquinone and menaquinone-4 concentrations in rat liver after oral, intravenous and intraperitoneal administration.

    PubMed

    Sakamoto, N; Kimura, M; Hiraike, H; Itokawa, Y

    1996-01-01

    To study the metabolism of K Vitamins (VK) in the liver, two types of natural VK, phylloquinone (K1) and menaquinone-4 (MK-4), were administered to male Wistar rats orally (P.O.), intravenously (I.V.) and intraperitoneally (I.P.). Blood and a small portion of the liver (and ascites by I.P.) were collected 8 times up to 72 h (P.O.) or 24 h (I.V. and I.P.). A modified assay procedure followed by high performance liquid chromatography (HPLC) was developed to detect VK from small amounts of liver tissue. After oral administration of both K1 and MK-4 (10 mumol/kg-P.O.), their concentrations in the liver increased from 1 h then reached a maximum at 6 h (10 nmol/g v.s. 0.35 nmol/g). After intravenous or intraperitoneal administration of K1 and MK-4 (0.5 mumol/kg-I.V. and I.P.), MK-4 concentrations in the liver reached a maximum faster than those of K1 (1.2 nmol/g -3 h vs. 1.3 nmol/g -0.5 h I.V. and 0.97 nmol/g -6 h vs. 0.47 nmol/g -1 h I.P.). MK-4 also increased in the liver from 6 h to 12 h (0.11 nmol/g -12 h) after oral administration of K1 (P.O.). These results indicate that K1 stays in plasma and liver longer than MK-4 and orally administered K1 might be transformed partially into MK-4 in the liver. PMID:8979160

  14. Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra-articular administration in healthy horses.

    PubMed

    Newman, J C; Prange, T; Jennings, S; Barlow, B M; Davis, J L

    2013-12-01

    The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra-articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half-life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax ) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0-2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on Cmax :MIC of 10. PMID:23531033

  15. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    PubMed

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration. PMID:25488714

  16. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  17. Pharmacokinetics of ricobendazole after its intravenous, intraruminal and subcutaneous administration in sheep.

    PubMed

    Formentini, E A; Mestorino, N; Errecalde, J O

    2005-10-01

    Ricobendazole (RBZ) was administered in sheep at the dose rate of 5 mg/kg by intravenous (i.v.) route as a 10% experimental solution, by the intraruminal (i.r.) route as a 10% experimental suspension, and by the subcutaneous (s.c.) route as a 10% commercial formulation available in Argentina. Blood samples were drawn during a 60 h period. Plasma concentrations of RBZ and its inactive metabolite albendazole sulphone (ABZSO2) were determined by high-performance liquid chromatography. The pharmacokinetic parameters were determined by compartmental analysis. The fitting of the data was done by weighted least-squares non-linear regression analysis. The pharmacokinetic parameters were estimated for every animal by simultaneous fitting of the plasma concentrations profiles of RBZ obtained after its administration by the three routes. The kinetic analysis of ABZSO2 was performed by a statistical moment approach. Ricobendazole bioavailability was poor after i.r. administration, whereas high and sustained plasma concentrations and higher bioavailability were obtained after s.c. administration. A simple two-compartment open model explains in a mechanical sense the pharmacokinetic behaviour of RBZ in sheep and allows us to estimate the real first-order constant rate of absorption and the loss of drug from the absorption site after its administration by s.c. and i.r. routes. PMID:16142607

  18. Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes

    PubMed Central

    Lim, Li Ying; Koh, Pei Yin; Somani, Sukrut; Al Robaian, Majed; Karim, Reatul; Yean, Yi Lyn; Mitchell, Jennifer; Tate, Rothwelle J.; Edrada-Ebel, RuAngelie; Blatchford, David R.; Mullin, Margaret; Dufès, Christine

    2015-01-01

    The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. From the Clinical Editor Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies. PMID:25933695

  19. Vitamin K1 distribution following intravenous vitamin K1-fat emulsion administration in rats.

    PubMed

    Xiao, Xue; Mi, Yan-Ni; Wang, Fa; Zhang, Bing-Hua; Cao, Lei; Cao, Yong-Xiao

    2015-12-01

    This study investigated vitamin K1 (VK1 ) distribution following intravenous vitamin K1-fat emulsion (VK1 -FE) administration and compared it with that after VK1 injection. Rats were intravenously injected with VK1-FE or VK1 . The organ and tissue VK1 concentrations were determined using high-performance liquid chromatography method at 0.5, 2 and 4 h to determine distribution, equilibrium and elimination phases, respectively. In the VK1-FE group, the plasma, heart and spleen VK1 concentrations decreased over time. However, other organs like liver, lung, kidney, muscle and testis, reached peak VK1 concentrations at 2 h. In the VK1 injection group, the liver VK1 concentrations were significantly higher than those in other organs at the three time points. However, VK1 concentrations in the other organs peaked at 2 h. In addition, in VK1-FE group, the heart, spleen and lung VK1 concentrations were significantly higher than those in the VK1 injection group at the three time points, and the liver VK1 concentration was significantly higher than that in the VK1 injection group at 4 h. The VK1 amount was greatest in the liver compared with the other organs. Thus, the liver is the primary organ for VK1 distribution. The distribution of VK1 is more rapid when injected as VK1-FE than as VK1 . PMID:25967735

  20. Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs.

    PubMed

    Kim, Eun-Young; Gebru, Elias; Lee, Joong-Su; Kim, Jong-Choon; Park, Seung-Chun

    2011-04-01

    A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs. PMID:21068517

  1. Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats.

    PubMed

    Aarde, Shawn M; Angrish, Deepshikha; Barlow, Deborah J; Wright, M Jerry; Vandewater, Sophia A; Creehan, Kevin M; Houseknecht, Karen L; Dickerson, Tobin J; Taffe, Michael A

    2013-09-01

    Recreational use of the drug 4-methylmethcathinone (mephedrone; 4-MMC) became increasingly popular in the United Kingdom in recent years, spurred in part by the fact that it was not criminalized until April 2010. Although several fatalities have been associated with consumption of 4-MMC and cautions for recreational users about its addictive potential have appeared on Internet forums, very little information about abuse liability for this drug is available. This study was conducted to determine if 4-MMC serves as a reinforcer in a traditional intravenous self-administration model. Groups of male Wistar and Sprague-Dawley rats were prepared with intravenous catheters and trained to self-administer 4-MMC in 1-hour sessions. Per-infusion doses of 0.5 and 1.0 mg/kg were consistently self-administered, resulting in greater than 80% discrimination for the drug-paired lever and mean intakes of about 2-3 mg/kg/hour. Dose-substitution studies after acquisition demonstrated that the number of responses and/or the total amount of drug self-administered varied as a function of dose. In addition, radiotelemetry devices were used to show that self-administered 4-MMC was capable of increasing locomotor activity (Wistar) and decreasing body temperature (Sprague-Dawley). Pharmacokinetic studies found that the T1/2 of 4-MMC was about 1 hour in vivo in rat plasma and 90 minutes using in vitro liver microsomal assays. This study provides evidence of stimulant-typical abuse liability for 4-MMC in the traditional pre-clinical self-administration model. PMID:23363010

  2. Efficacy and safety of intravenous nimodipine administration for treatment of hypertension in patients with intracerebral hemorrhage

    PubMed Central

    Li, Yuqian; Fang, Wei; Tao, Lei; Li, Min; Yang, Yanlong; Gao, Yafei; Ge, Shunnan; Gao, Li; Zhang, Bin; Li, Zhihong; Zhou, Wei; Wang, Boliang; Li, Lihong

    2015-01-01

    Background Nicardipine (NC) is the most commonly used antihypertensive drug in neurological patients with hypertension. Although nimodipine (NM) is widely used to treat cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage, trials exploring its antihypertensive effect after intravenous administration in subjects with intracerebral hemorrhage (ICH) are scarce. Methods A retrospective study was carried out to compare the safety and efficacy of NC and NM administered intravenously in patients with ICH. Therapeutic responses were assessed by achievement of goal blood pressure (BP); use of additional medications for BP control; proportion of time spent within goal; variability in BP; time to goal BP; number of dose adjustments; variability in ICH volume, Glasgow Coma Scale score, and intracranial pressure; and drug-related complications. Results A total of 87 patients were eligible for analysis (n=46 [NC]; n=41 [NM]), and baseline characteristics between groups were similar. Both agents were effective in achieving goal BP during infusion, with 93.5% and 87.8% patients in the NC and NM groups achieving goal, respectively. Fewer additional medications were needed to control BP in the NC group. BP variability was similar and no differences were observed in the mean time to goal BP and mean numbers of dose adjustments between both groups. Interestingly, intracranial pressure declined (P=0.048) during NC administration but increased (P=0.066) after NM treatment. Finally, the incidences of hematoma expansion, neurological deterioration, and adverse drug events were similar in both groups. Conclusion NM is effective and safe for BP control in patients with ICH. PMID:26056454

  3. Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats

    PubMed Central

    Aarde, S. M.; Angrish, D.; Barlow, D.J.; Wright, M. J.; Vandewater, S. A.; Creehan, K.M.; Houseknecht, K. L.; Dickerson, T. J.; Taffe, M. A.

    2013-01-01

    Recreational use of the drug 4-methylmethcathinone (mephedrone; 4-MMC) became increasingly popular in the United Kingdom in recent years, spurred in part by the fact it was not criminalized until April of 2010. Although several fatalities have been associated with consumption of 4-MMC and cautions for recreational users about its addictive potential have appeared on Internet forums, very little information about abuse liability for this drug is available. This study was conducted to determine if 4-MMC serves as a reinforcer in a traditional intravenous self-administration model. Groups of male Wistar and Sprague-Dawley rats were prepared with intravenous catheters and trained to self-administer 4-MMC in one hour sessions. Per infusion doses of 0.5 and 1.0 mg/kg were consistently self-administered resulting in greater than 80% discrimination for the drug-paired lever and mean intakes of about 2–3 mg/kg/hr. Dose-substitution studies after acquisition demonstrated that the number of responses and/or the total amount of drug self-administered varied as a function of dose. In addition, radiotelemetry devices were employed to show that self-administered 4-MMC was capable of increasing locomotor activity (Wistar) and decreasing body temperature (Sprague-Dawley). Pharmacokinetic studies found the T1/2 of 4-MMC was about an hour in vivo in rat plasma and 90 minutes using in vitro liver microsomal assays. This study provides evidence of stimulant-typical abuse liability for 4-MMC in the traditional preclinical self-administration model. PMID:23363010

  4. Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration.

    PubMed

    Anfossi, P; Malvisi, J; Catraro, N; Bolognini, M; Tomasi, L; Stracciari, G L

    1993-01-01

    Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t1/2 alpha: 11.13 +/- 3.76 min; t1/2 beta: 71.98 +/- 24.75 min; MRT 70.69 +/- 11.97 min). Benzydamine was widely distributed in the body fluids and tissues (Vd(area): 3.549 +/- 1.301 L/kg) and characterized by a high value for body clearance (33.00 +/- 5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, the Cmax value was 38.13 +/- 4.2 ng/ml at a tmax of 67.13 +/- 4.00 min; MAT and MRT were 207.33 +/- 22.64 min and 278.01 +/- 12.22 min, respectively. Benzydamine bioavailability was very high (92.07% +/- 7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34 +/- 86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment. PMID:8146956

  5. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys.

    PubMed

    Mao, Cheng-Ping; Brovarney, Martin R; Dabbagh, Karim; Birnböck, Herbert F; Richter, Wolfgang F; Del Nagro, Christopher J

    2013-01-01

    The CD20-specific monoclonal antibody rituximab (MabThera(®), Rituxan(®)) is widely used as the backbone of treatment for patients with hematologic disorders. Intravenous administration of rituximab is associated with infusion times of 4-6 hours, and can be associated with infusion-related reactions. Subcutaneous administration of rituximab may reduce this and facilitate administration without infusion-related reactions. We sought to determine the feasibility of achieving equivalent efficacy (measured by endogenous B-cell depletion) and long-term durability of CD20 target coverage for subcutaneously administered rituximab compared with intravenous dosing. In these preclinical studies, male cynomolgus monkeys were treated with either intravenous rituximab or novel subcutaneous formulation of rituximab containing human recombinant DNA-derived hyaluronidase enzyme. Peripheral blood samples were analyzed for serum rituximab concentrations, peripheral B-cell depletion, and CD20 target coverage, including subset analysis according to CD21+ status. Distal lymph node B-cell depletion and CD20 target coverage were also measured. Initial peak serum concentrations of rituximab were significantly higher following intravenous administration than subcutaneous. However, the mean serum rituximab trough concentrations were comparable at 2 and 7 days post-first dose and 9 and 14 days post-second dose. Efficacy of B-cell depletion in both peripheral blood and distal lymph nodes was comparable for both methods. In lymph nodes, 9 days after the second dose with subcutaneous and intravenous rituximab, B-cell levels were decreased by 57% and 42% respectively. Similarly, levels of peripheral blood B cells were depleted by >94% for both subcutaneous and intravenous dosing at all time points. Long-term recovery of free unbound surface CD20 levels was similar, and the duration of B-cell depletion was equally sustained over 2 months for both methods. These results demonstrate that, despite

  6. Subcutaneous versus Intravenous Administration of Rituximab: Pharmacokinetics, CD20 Target Coverage and B-Cell Depletion in Cynomolgus Monkeys

    PubMed Central

    Mao, Cheng-Ping; Brovarney, Martin R.; Dabbagh, Karim; Birnböck, Herbert F.; Richter, Wolfgang F.; Del Nagro, Christopher J.

    2013-01-01

    The CD20-specific monoclonal antibody rituximab (MabThera®, Rituxan®) is widely used as the backbone of treatment for patients with hematologic disorders. Intravenous administration of rituximab is associated with infusion times of 4–6 hours, and can be associated with infusion-related reactions. Subcutaneous administration of rituximab may reduce this and facilitate administration without infusion-related reactions. We sought to determine the feasibility of achieving equivalent efficacy (measured by endogenous B-cell depletion) and long-term durability of CD20 target coverage for subcutaneously administered rituximab compared with intravenous dosing. In these preclinical studies, male cynomolgus monkeys were treated with either intravenous rituximab or novel subcutaneous formulation of rituximab containing human recombinant DNA-derived hyaluronidase enzyme. Peripheral blood samples were analyzed for serum rituximab concentrations, peripheral B-cell depletion, and CD20 target coverage, including subset analysis according to CD21+ status. Distal lymph node B-cell depletion and CD20 target coverage were also measured. Initial peak serum concentrations of rituximab were significantly higher following intravenous administration than subcutaneous. However, the mean serum rituximab trough concentrations were comparable at 2 and 7 days post-first dose and 9 and 14 days post-second dose. Efficacy of B-cell depletion in both peripheral blood and distal lymph nodes was comparable for both methods. In lymph nodes, 9 days after the second dose with subcutaneous and intravenous rituximab, B-cell levels were decreased by 57% and 42% respectively. Similarly, levels of peripheral blood B cells were depleted by >94% for both subcutaneous and intravenous dosing at all time points. Long-term recovery of free unbound surface CD20 levels was similar, and the duration of B-cell depletion was equally sustained over 2 months for both methods. These results demonstrate that, despite

  7. Formulation and stability of busulfan for intravenous administration in high-dose chemotherapy.

    PubMed

    Bhagwatwar, H P; Phadungpojna, S; Chow, D S; Andersson, B S

    1996-01-01

    The bifunctional alkylating agent busulfan (Bu) was solubilized in a cosolvent mixture of anhydrous dimethylacetamide (DMA), polyethylene glycol 400 (PEG400), and water at a ratio of 1:2:2 (v/v/v), to achieve a Bu concentration of 3 mg/ml, a preparation that would be suitable for parenteral administration in high-dose chemotherapy preceding bone marrow transplantation. The complete formulation was stable for more than 54 h at room temperature (RT, 22 degrees C). An accelerated stability study of Bu in anhydrous DMA or DMA/PEG400 (1:2) as stock solutions indicated shelf-lives of 191 and 180 days respectively, at RT, and 8.2 and 7.5 years, respectively, at 4 degrees C. Although the complete formulation with Bu was very hypertonic, hemolysis studies indicated that the formulation would be safe for intravenous (i.v.) administration, since it would be rapidly diluted to harmless tonicity levels in the blood. Cytotoxicity studies of the complete formulation in vitro proved that Bu retained its activity when dissolved in the complete vehicle. A preliminary pharmacokinetic study in a rodent model after the i.v. administration of Bu at a dose of 1 mg/kg body weight yielded high plasma concentrations of Bu for at least 5 h after injection. PMID:8599861

  8. Addressing Concerns about Changing the Route of Antimicrobial Administration from Intravenous to Oral in Adult Inpatients

    PubMed Central

    Béïque, Lizanne; Zvonar, Rosemary

    2015-01-01

    Background: Many health care institutions are in the process of establishing antimicrobial stewardship programs. Changing the route of administration of antimicrobial agents from intravenous to oral (IV to PO) is a simple, well-recognized intervention that is often part of an antimicrobial stewardship program. However, the attending health care team may have concerns about making this switch. Objectives: To provide insights into common concerns related to IV to PO conversion, with the aim of helping antimicrobial stewardship teams to address them. Data Sources: Published clinical trials and reviews were identified from a literature search of Ovid MEDLINE with the keywords (step down or switch or conversion or transition or sequential) and (antibiotics or antibacterial agents or antimicrobial or anti-infective agents). Data Synthesis: The following issues are addressed in this review: benefits of the oral route, serum concentrations yielded by the oral formulation, source of pharmacokinetic data, clinical outcomes, provision of care in the intensive care unit, fear of therapeutic failure, and administration of antimicrobials via feeding tube. Conclusions: When considering a change to oral therapy, it is important to have a thorough understanding of key aspects of the antimicrobial agent, the patient, and the disease being treated. The antimicrobial stewardship team has an important role in facilitating IV to PO conversion, educating prescribers, and addressing any concerns or reservations that may interfere with timely transition from IV to PO administration. PMID:26327706

  9. Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration

    PubMed Central

    Jochemsen, Roeline; Wesselman, J. G. J.; Hermans, J.; van Boxtel, C. J.; Breimer, D. D.

    1983-01-01

    1 Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. 2 Kinetic parameters after i.v. administration were: volume of distribution 0.66 ± 0.19 1/kg, total plasma clearance 113 ± 28 ml/min, distribution half-life 11 ± 6 min, and elimination half-life 4.8 ± 1.4 h (mean values ± s.d.). 3 Kinetic parameters after oral administration were: absorption lag-time 8 ± 12 min, absorption half-life 10 ± 11 min, and elimination half-life 5.1 ± 1.2 h (mean values ± s.d.). 4 Bioavailability of brotizolam was 70 ± 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 ± 24% (range: 47-117%). PMID:6661374

  10. Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications.

    PubMed

    Ding, H Z; Yang, G X; Huang, X H; Chen, Z L; Zeng, Z L

    2008-06-01

    Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t(1/2beta)) were 17.14 +/- 4.14, 25.79 +/- 8.10, 16.67 +/- 4.04 (pigs) and 6.11 +/- 1.50, 5.64 +/- 0.74, 8.20 +/- 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (C(max)) of 1.77 +/- 0.66, 2.29 +/- 0.85 (pigs) and 2.51 +/- 0.36, 1.00 +/- 0.21 microg/mL (broilers) attained at t(max) of 1.29 +/- 0.26, 1.41 +/- 0.88 (pigs) and 0.86 +/- 0.4, 4.34 +/- 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 +/- 28.9)% and (105.7 +/- 37.1)% (pigs) and (77.0 +/- 11.8)% and (54.2 +/- 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(V(d(area))) of 4.91 +/- 1.88 and 3.10 +/- 0.67 L/kg and total body clearances(Cl(B)) of 0.20 +/- 0.06 and 0.37 +/- 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t(1/2ka), t(1/2alpha)) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC(90) are <0.25 microg/mL and <0.1 microg/mL respectively. PMID:18471140

  11. Michaelis-Menten elimination kinetics of etanercept, rheumatoid arthritis biologics, after intravenous and subcutaneous administration in rats.

    PubMed

    Lee, Byung-Yo; Kwon, Kwang-Il; Kim, Min-Soo; Baek, In-Hwan

    2016-08-01

    Etanercept was approved by the Food and Drug Administration (FDA) in 2010 as a biologic agent for the treatment of rheumatoid arthritis (RA). The aim of the study was to investigate the pharmacokinetic properties of etanercept after intravenous and subcutaneous injection in rats. The plasma concentration of etanercept was determined using an enzyme-linked immunosorbent assay (ELISA). Intravenous and subcutaneous administration of 2 mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max] = 1.60 days, bioavailability [F] = 47.18 %) and slowly eliminated (half-life [t 1/2], 2.33 days after intravenous administration and 3.31 days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25 ± 14.37 and 48.56 ± 6.78 μg day/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max = 94.28 µg/day; K m = 10.88 µg/mL) was used to describe the pharmacokinetic profile of etanercept. Our results describe the pharmacokinetic profile of etanercept, and these results could be used for the development of etanercept biosimilars. PMID:25725773

  12. Intravenous Administration of Simvastatin Improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats.

    PubMed

    Mountney, Andrea; Boutté, Angela M; Gilsdorf, Janice; Lu, Xi-Chun; Tortella, Frank C; Shear, Deborah A

    2016-08-15

    Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. The beneficial effects of oral simvastatin have been reported in pre-clinical models of traumatic brain injury (TBI). The current study was designed to evaluate the potential beneficial effects of simvastatin in a model of severe penetrating TBI using an intravenous (IV) route of administration. Rats were subjected to unilateral frontal penetrating ballistic-like brain injury (PBBI), and simvastatin was delivered intravenously at 30 min and 6 h post-injury and continued once daily for either 4 or 10 days post-PBBI. Motor function was assessed on the rotarod and cognitive performance was evaluated using the Morris water maze (MWM) task. Serum levels of inflammatory cytokines and the astrocytic biomarker, glial fibrillary acidic protein (GFAP), were quantified at 1 h, 4 h, and 24 h post-injury. Histopathological damage was assessed at the terminal end-point. Rotarod testing revealed significant motor deficits in all injury groups but no significant simvastatin-induced therapeutic benefits. All PBBI-injured animals showed cognitive impairment on the MWM test; however, 10-day simvastatin treatment mitigated these effects. Animals showed significantly improved latency to platform and retention scores, whereas the 4-day treatment regimen failed to produce any significant improvements. Biomarker and cytokine analysis showed that IV simvastatin significantly reduced GFAP, interleukin (IL)-1α, and IL-17 serum levels by 4.0-, 2.6-, and 7.0-fold, respectively, at 4 h post-injury. Collectively, our results demonstrate that IV simvastatin provides significant protection against injury-induced cognitive dysfunction and reduces TBI-specific biomarker levels. Further research is warranted to identify the optimal dose and therapeutic window for IV delivery of simvastatin in models of severe TBI. PMID:26542887

  13. The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration.

    PubMed

    Davis, J L; Papich, M G; Weingarten, A

    2006-06-01

    The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high-pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determined in vitro. Following i.v. administration, orbifloxacin had a terminal half-life (t1/2) of 5.08 h and a volume of distribution (V(d(SS))) of 1.58 L/kg. Following oral administration, the average maximum plasma concentration (Cmax) was 1.25 microg/mL with a t1/2 of 3.42 h. Systemic bioavailability was 68.35%. Plasma protein binding was 20.64%. The octanol:water partition coefficient (pH 7.4) was 0.2 +/- 0.11. No adverse reactions were noted during this study. Dosage regimens were determined from the pharmacokinetic-pharmacodynamic parameters established for fluoroquinolone antibiotics. For susceptible bacteria, an oral dose of approximately 5 mg/kg once daily will produce plasma concentrations within the suggested range. This dose is suggested for further studies on the clinical efficacy of orbifloxacin for treatment of susceptible bacterial infections in the horse. PMID:16669863

  14. Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration in Hanwoo, Korean native cattle.

    PubMed

    Belew, Sileshi; Kim, Jin-Yoon; Hossain, Md Akil; Park, Ji-Yong; Lee, Seung-Jin; Park, Yong-Soo; Suh, Joo-Won; Kim, Jong-Choon; Park, Seung-Chun

    2015-03-01

    Pharmacokinetic (PK) parameters of marbofloxacin (MRFX) in Korean cattle, Hanwoo, were determined following its intravenous (i.v.) or intramuscular (i.m.) administration at a dose of 2 mg/kg. Area under the curve (AUC0-24 hr), half-life (t1/2) and total body clearance (CLB) of i.v. MRFX were 6.87 hr∙µg/ml, 2.44 hr and 0.29 l/kg∙hr, respectively, and the corresponding values for i.m. administration of MRFX were 5.07 hr∙µg/ml, 2.44 hr and 0.39 l/kg∙hr. The suggested optimal doses of MRFX in Hanwoo cattle, calculated by integration of PK data obtained in the present study and previously reported minimum inhibitory concentration (MIC) for MRFX against susceptible (MIC ≤1 µg/ml) and intermediate (MIC ≤2 µg/ml) pathogenic bacteria, were 2.1 and 4.2 mg/kg/day by i.v. route and 3.9 and 7.8 mg/kg/day by i.m. route. PMID:25411109

  15. Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration in Hanwoo, Korean native cattle

    PubMed Central

    BELEW, Sileshi; KIM, Jin-Yoon; HOSSAIN, Md.Akil; PARK, Ji-Yong; LEE, Seung-Jin; PARK, Yong-Soo; SUH, Joo-Won; KIM, Jong-Choon; PARK, Seung-Chun

    2014-01-01

    Pharmacokinetic (PK) parameters of marbofloxacin (MRFX) in Korean cattle, Hanwoo, were determined following its intravenous (i.v.) or intramuscular (i.m.) administration at a dose of 2 mg/kg. Area under the curve (AUC0–24 hr), half-life (t1/2) and total body clearance (CLB) of i.v. MRFX were 6.87 hr∙µg/ml, 2.44 hr and 0.29 l/kg∙hr, respectively, and the corresponding values for i.m. administration of MRFX were 5.07 hr∙µg/ml, 2.44 hr and 0.39 l/kg∙hr. The suggested optimal doses of MRFX in Hanwoo cattle, calculated by integration of PK data obtained in the present study and previously reported minimum inhibitory concentration (MIC) for MRFX against susceptible (MIC ≤1 µg/ml) and intermediate (MIC ≤2 µg/ml) pathogenic bacteria, were 2.1 and 4.2 mg/kg/day by i.v. route and 3.9 and 7.8 mg/kg/day by i.m. route. PMID:25411109

  16. Liver lipid composition and intravenous, intraperitoneal, and enteral administration of intralipid.

    PubMed

    Morán Penco, J M; Maciá Botejara, E; Salas Martinez, J; Mahedero Ruiz, G; Climent Mata, V; Saenz de Santamaria, J; Vinagre Velasco, L M

    1994-01-01

    We studied the variations arising in plasma and liver lipids after intravenous (i.v.), intraperitoneal (IP), and intragastric (IG) administration of a fat overdose on the order of 4 g.kg-1 body wt.day-1 in the form of Intralipid (ITL) 20% to 33 New Zealand rabbits for 15 days. The control group was submitted for surgery but did not receive an ITL supplement. The results show weight gain in all animals and normal liver enzyme values. There was an increase in plasma lipids in groups supplemented by the parenteral route (i.v. and IP), and fatty acids showed a similar distribution, in terms of percentages, to that for ITL. In liver tissue, there was an increase in the fractions related to ethanolamine and a decrease in phospholipids of choline and serine. In the i.v. group, neutral lipids predominated compared with other groups. The livers of all supplemented animals (i.v., IP, and IG) showed a higher content of stearic and linoleic acid and a reduction in oleic acid. Study with optical microscopy showed a microvacuolization affecting the three areas of the hepatic acini in the i.v. group, seen with electron microscopy as vacuoles lacking membranes and surrounded by mitochondria. In conclusion, there is an increase in hepatic steatosis in parenteral groups and a greater deposit of neutral lipids in the i.v. group, related to the administration route, without biochemical signs of liver dysfunction. PMID:8199419

  17. In vivo behavior of MIL-100 nanoparticles at early times after intravenous administration.

    PubMed

    Simon-Yarza, T; Baati, T; Neffati, F; Njim, L; Couvreur, P; Serre, C; Gref, R; Najjar, M Fadhel; Zakhama, A; Horcajada, P

    2016-09-25

    Metal-organic frameworks have shown interesting features for biomedical applications, such as drug delivery and imaging agents. The benchmarked mesoporous iron(III) trimesate MIL-100 MOF nanocarrier combines progressive release of high drug cargoes with absence of visible in vivo toxicity. Although in a previous study pharmacokinetics and biodistribution of MIL-100 nanoparticles were evaluated in the long term (from 24h to 1 month), the crucial times for drug targeting and delivery applications are shorter (up to 24h). Thus, this work aims to study the blood circulating profile and organ accumulation of MIL-100 nanocarrier at early times after administration. For this purpose, after intravenous administration to rats, both constitutive components of MIL-100 (trimesate and iron) were quantified by high performance liquid chromatography and a spectrophotometric method, respectively. The pharmacokinetic profile suggested that the nanoparticles act as a depot in the blood stream during the first hours before being cleared. Accumulation took mainly place in the liver and, in some extent, in the spleen. Nevertheless, histological studies demonstrated the absence of morphological alterations due to the presence of the particles in these organs. Liver function was however slightly altered as reflected by the increased plasma aspartate aminotransferase concentrations. Finally trimesate was progressively eliminated in urine. PMID:27515292

  18. Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats

    PubMed Central

    Miller, ML; Aarde, SM; Moreno, AY; Creehan, KM; Janda, KD; Taffe, MA

    2015-01-01

    BACKGROUND D-methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats. METHODS Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1 mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20 mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15 mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30 min after an acute challenge dose of 3.2 mg/kg METH. RESULTS Active vaccination inhibited the acquisition of METH self-administration under the 0.1 mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05 mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers. CONCLUSIONS These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration. PMID:26118833

  19. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

    2011-09-01

    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus

  20. EFFECTS OF CHLORDIMEFORM ON CARDIOVASCULAR FUNCTIONAL PARAMETERS. PART 2. ACUTE AND DELAYED EFFECTS FOLLOWING INTRAVENOUS ADMINISTRATION IN THE POSTWEANLING RAT

    EPA Science Inventory

    The differential effects of intravenous (IV) intraperitoneal (IP) administration of chlordimeform (CDM) were investigated in 22-30 day old pentobarbital-anesthetized Sprague-Dawley rats. The first group of animals (N=25) were given sequential IV injections of 5, 10, 30, 60, and 1...

  1. Effect of intravenous or oral sodium chlorate administration on the fecal shedding of Escherichia coli in sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 +/- 2.5 kg) were administered 150 mg NaClO3 per kg BW by gavage or i.v. infusion in a cross-over design with sal...

  2. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    PubMed Central

    Jin, Jing-fen; Zhu, Ling-ling; Chen, Meng; Xu, Hui-min; Wang, Hua-fen; Feng, Xiu-qin; Zhu, Xiu-ping; Zhou, Quan

    2015-01-01

    Background Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods. Methods A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies. Results “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immu-noglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and

  3. Intravenous self-administration of gamma-hydroxybutyrate (GHB) in baboons

    PubMed Central

    Goodwin, Amy K.; Kaminski, Barbara J.; Griffiths, Roland R.; Ator, Nancy A.; Weerts, Elise M.

    2010-01-01

    Background Abuse of gamma-hydroxybutyrate (GHB) poses a public health concern. In previous studies, intravenous (IV) self-administration of GHB doses up to 10 mg/kg was not maintained in non-human primates under limited-access conditions, which was inconsistent with the usual good correspondence between drugs abused by humans and those self-injected by laboratory animals. Methods Self-administration of GHB was studied in 10 baboons using procedures standard for our laboratory to assess drug abuse liability. Each self-injection depended on completion of 120 or 160 lever responses. Sessions ran continuously; a 3-h timeout limited the number of injections per 24 h to 8. Self-injection was established at 6–8 injections/day with cocaine (0.32 mg/kg/injection) prior to substitution of each GHB dose (3.2–178 mg/kg/injection) or vehicle for 15 days. Food pellets were available 24 h/day. Results GHB maintained significantly greater numbers of injections when compared to vehicle in 6 of the 9 baboons that completed GHB evaluations that included 32 mg/kg/injection or higher. The baboons that self-administered GHB at high rates were ones for which GHB was the first drug each had tested under the 24-hr/day cocaine baseline procedure. Self-injection of the highest doses of GHB decreased food-maintained responding. Conclusions High-dose GHB can function as a reinforcer in non-human primates under 24-h access, but self-administration history may be important. The findings are consistent with the demonstrated abuse liability of GHB in humans, and remove GHB as an exception to the typical good correspondence between those drugs abused by humans and those self-administered by nonhuman primates. PMID:21112162

  4. Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

    PubMed

    Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

    2016-07-01

    Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration. PMID:26717881

  5. Incompatibilities of lornoxicam with 4 antiemetic medications in polyolefin bags during simulated intravenous administration.

    PubMed

    Fang, Bao-Xia; Li, Peng; Shi, Xiao-Ya; Chen, Fu-Chao; Wang, Lin-Hai

    2016-06-01

    The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration.In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis.No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations.The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C. PMID:27336868

  6. Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration.

    PubMed

    Ellefsen, Kayla N; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2016-03-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  7. Incompatibilities of lornoxicam with 4 antiemetic medications in polyolefin bags during simulated intravenous administration

    PubMed Central

    Fang, Bao-xia; Li, Peng; Shi, Xiao-ya; Chen, Fu-chao; Wang, Lin-hai

    2016-01-01

    Abstract The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration. In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis. No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations. The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C. PMID:27336868

  8. Alterations in the striatal dopamine system during intravenous methamphetamine exposure: effects of contingent and noncontingent administration.

    PubMed

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P

    2013-08-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long-term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a "humanized" plasma METH half life or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7 and 1.5 µM. Animals were sacrificed during their last METH administration for autoradiography assessment using [³H]ligands and D2 agonist-induced [³⁵S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15-20%) and [³⁵S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal's total intake was similar within and across three 24-h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. PMID:23417852

  9. Alterations in the Striatal Dopamine System During Intravenous Methamphetamine Exposure: Effects of Contingent and Noncontingent Administration

    PubMed Central

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P.

    2014-01-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a ‘humanized’ plasma METH half life, or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7–1.5 μM. Animals were sacrificed during their last METH administration for autoradiography assessment using [3H]ligands and D2 agonist-induced [35S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15–20%) and [35S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal’s total intake was similar within and across three 24 h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. PMID:23417852

  10. [Hplc estimation of coenzyme Q(10) redox status in plasma after intravenous coenzyme Q(10) administration].

    PubMed

    Kalenikova, E I; Kharitonova, E V; Gorodetskaya, E A; Tokareva, O G; Medvedev, O S

    2015-01-01

    The pharmacokinetics of the total pool of coenzyme Q(10) (Co(10)), its oxidized (ubiquinone) and reduced (ubiquinol, CoQ(10)H₂) forms have been investigated in rats plasma during 48 h after a single intravenous injection of a solution of solubilized CoQ(10) (10 mg/kg) to rats. Plasma levels of CoQ(10) were determined by HPLC with spectrophotometric and coulometric detection. In plasma samples taken during the first minutes after the CoQ(10) intravenous injection, the total pool of coenzyme Q(10) and proportion of CoQ(10)H₂ remained unchanged during two weeks of storage at -20°C. The kinetic curve of the total pool of coenzyme Q(10) corresponds to a one-part model (R² = 0.9932), while the corresponding curve of its oxidized form fits to the two-part model. During the first minutes after the injection a significant portion of plasma ubiquinone undergoes reduction, and after 7 h the concentration of ubiquinol predominates. The decrease in the total plasma coenzyme Q(10) content was accompanied by the gradual increase in plasma ubiquinol, which represented about 90% of total plasma CoQ(10) by the end of the first day. The results of this study demonstrate the ability of the organism to transform high concentrations of the oxidized form of CoQ(10) into the effective antioxidant (reduced) form and justify prospects of the development of parenteral dosage forms of CoQ(10) for the use in the treatment of acute pathological conditions. PMID:25762606

  11. Toxicity of Hexamoll(®) DINCH(®) following intravenous administration.

    PubMed

    David, Raymond M; White, Randy D; Larson, Michael J; Herman, Jay K; Otter, Rainer

    2015-10-14

    Alternative plasticizers to di(2-ethylhexyl) phthalate (DEHP) for blood bags have been sought for many years. Cyclohexane-1,2-dicarboxylic acid, diisononylester (Hexamoll(®) DINCH(®)) is an alternative that has been evaluated in preliminary studies for compatibility and efficacy to preserve whole blood. While Hexamoll(®) DINCH(®) has an extensive database for mammalian toxicity via oral administration, data were needed to evaluate toxicity from intravenous (IV) administration to support the use of the plasticizer Hexamoll(®) DINCH(®) in blood bags. A series of studies was performed by slow IV injection or IV infusion of Hexamoll(®) DINCH(®), a highly viscous, hydrophobic substance, suspended in Intralipid(®) 20% (20% intravenous fat emulsion). Rats were injected once, followed by 14 days of recovery; injected daily for 5 days followed by 5 days of recovery, or infused for 29 days (4h/day) followed by 14 days of recovery. Dose levels were 0, 62, 125, and 250-300mg/kg body weight/day. These dose levels represent the limits of suspension and far exceed any anticipated exposures from migration out of plasticized blood bags. Animals were observed for signs of toxicity; body weight and feed consumption were measured; blood collected for clinical chemistry and hematology; and tissues collected and processed for histopathology. Special emphasis was placed on evaluating endpoints and tissues that are commonly associated with plasticizer exposure in rodents. Urine was collected during the 4-week study to quantify urinary metabolites of Hexamoll(®) DINCH(®). The results of the studies indicate that no substance-related toxicity occurred: no effects on behavior, no effects on organ weight, no effect on serum chemistry including thyroid hormones; and no effect on major organs, especially no testicular toxicity and no indication for peroxisome proliferation in the liver. The only effects seen were petechia and granulomas related to dissipation of suspended Hexamoll

  12. Pharmacokinetic Interpretation of Blood Levels and Urinary Excretion Data for Cefazolin and Cephalothin After Intravenous and Intramuscular Administration in Humans

    PubMed Central

    Rattie, Elisabeth S.; Ravin, Louis J.

    1975-01-01

    Blood levels of cefazolin and cephalothin were determined in two separate crossover studies in 20 healthy male adults, each after intravenous and intramuscular administration. Pharmacokinetic parameters were calculated from the intravenous data based upon a two-compartment open model. The rate constants controlling the distribution between the central and peripheral compartments, the overall elimination rate constants, the apparent volumes of distribution, and the fraction of the dose in the central and peripheral compartments were determined. The bioavailability was calculated to be 100% for cefazolin and cephalothin. PMID:1147591

  13. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

    PubMed Central

    Lee, Kwang-Ho; Yu, JunSang; Sun, Seungho; Kwon, KiRok

    2015-01-01

    Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP) is used. Thus, sweet bee venom (SBV) was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal). Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats. PMID:26389001

  14. Compatibility of Cloxacillin Sodium with Selected Intravenous Drugs During Simulated Y-Site Administration

    PubMed Central

    Sullivan, Thomas; Forest, Jean-Marc

    2015-01-01

    Abstract Background: Data regarding Y-site compatibility of intravenous (IV) cloxacillin sodium with other drugs are scarce and incomplete. Objective: To establish the compatibility of IV cloxacillin with 89 injectable drugs during simulated Y-site administration. Methods: Cloxacillin sodium (10 mL, 100 mg/mL) was combined with 89 undiluted IV drugs (10 mL, each). Tests were duplicated and performed at room temperature. Visual evaluation and a light obscuration particle count test were performed on 1 of the 2 solutions immediately after mixing. The second mixture underwent visual evaluation after 15 minutes, 1 hour, and 4 hours, followed by a particle count test at 4 hours. Drugs were considered incompatible if the mixture precipitated or became turbid within the 4-hour period or exceeded the particle count limit allowed by Test 1.B of USP <788> initially or at 4 hours. Results: Of the 89 tested drugs, 64 were compatible for up to 4 hours. The remaining 25 drugs were incompatible. Of these incompatible drugs, 16 were identified visually, and 9 were identified by the light obscuration particle count test. Conclusions: Sixty-four IV drugs were found to be compatible with cloxacillin via simulated Y-site, whereas 25 drugs were found to be incompatible with the antibiotic. The light obscuration particle count test should be used to complement visual evaluation when samples do not precipitate immediately. PMID:26405311

  15. Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats.

    PubMed

    Zhang, Chao; Cui, Xiangyong; Yang, Yan; Gao, Feng; Sun, Yantong; Gu, Jingkai; Fawcett, J Paul; Yang, Wei; Wang, Wei

    2011-04-01

    Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new water-soluble salt of felbinac currently undergoing clinical evaluation as an intravenous (i.v.) formulation for the treatment of severe post-operative pain. This article reports the pharmacokinetics of felbinac after i.v. administration of felbinac trometamol in Sprague-Dawley rats. The maximum plasma concentration (C(0)) and area under the plasma concentration-time curve (AUC) of felbinac administered at doses of 3.36, 8.40 and 21.0 mg/kg felbinac trometamol increased linearly with dose. Felbinac was highly protein bound (~95%) at plasma concentrations up to 75 μg/ml and extensively metabolized with only small amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile (0.465%). 4'-Hydroxyfelbinac was the principal metabolite in urine, feces and bile together with felbinac glucuronide, 4'-hydroxyfelbinac glucuronide and sulfate. The majority of the administered dose was excreted in urine (63.6%) mostly as 4'-hydroxyfelbinac. Total drug in urine and feces accounted for about 72% of the dose. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation. PMID:21182394

  16. Pharmacokinetic study of indocyanine Green after intravenous administration by UPLC-MS/MS

    PubMed Central

    Chen, Yu; Chen, Dongxin; Hu, Wenhao; Lin, Guanyang; Huang, Shiyong

    2015-01-01

    Indocyanine Green is widely used in medical diagnosis and to evaluate liver function and other regional blood flows in clinical application or animal experiments. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of Indocyanine Green in rat plasma was developed and validated. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 753.4→330.2 for Indocyanine Green, and m/z 611.1→303.1 for IS. Calibration plots were linear throughout the range 20-5000 ng/mL for Indocyanine Green in rat plasma. Mean recoveries of Indocyanine Green in rat plasma ranged from 79.5% to 85.4%. RSD of intra-day and inter-day precision were both < 12%. The accuracy of the method was between 95.9% and 113.9%. The method was successfully applied to pharmacokinetic study of Indocyanine Green after intravenous administration. PMID:26629038

  17. Pharmacokinetics of azithromycin in the blue and gold macaw (Ara ararauna) after intravenous and oral administration.

    PubMed

    Carpenter, James W; Olsen, John H; Randle-Port, Mary; Koch, David E; Isaza, Ramiro; Hunter, Robert P

    2005-12-01

    Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended. PMID:17312716

  18. Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

    PubMed

    Ferreira, Luana M; Cervi, Verônica F; Gehrcke, Mailine; da Silveira, Elita F; Azambuja, Juliana H; Braganhol, Elizandra; Sari, Marcel H M; Zborowski, Vanessa A; Nogueira, Cristina W; Cruz, Letícia

    2015-06-01

    This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma. PMID:25935266

  19. Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms.

    PubMed

    León, Guillermo; Herrera, María; Segura, Álvaro; Villalta, Mauren; Vargas, Mariángela; Gutiérrez, José María

    2013-12-15

    Snake antivenoms are formulations of immunoglobulins, or immunoglobulin fragments, purified from the plasma of animals immunized with snake venoms. Their therapeutic success lies in their ability to mitigate the progress of toxic effects induced by snake venom components, when administered intravenously. However, due to diverse factors, such as deficient manufacturing practices, physicochemical characteristics of formulations, or inherent properties of heterologous immunoglobulins, antivenoms can induce undesirable adverse reactions. Based on the time lapse between antivenom administration and the onset of clinical manifestations, the World Health Organization has classified these adverse reactions as: 1 - Early reactions, if they occur within the first hours after antivenom infusion, or 2 - late reactions, when occurring between 5 and 20 days after treatment. While all late reactions are mediated by IgM or IgG antibodies raised in the patient against antivenom proteins, and the consequent formation of immune complexes, several mechanisms may be responsible for the early reactions, such as pyrogenic reactions, IgE-mediated reactions, or non IgE-mediated reactions. This work reviews the hypotheses that have been proposed to explain the mechanisms involved in these adverse reactions to antivenoms. The understanding of these pathogenic mechanisms is necessary for the development of safer products and for the improvement of snakebite envenomation treatment. PMID:24055551

  20. Effect of infusion rate on intravenous nicotine self-administration in rats.

    PubMed

    Wing, Victoria C; Shoaib, Mohammed

    2013-09-01

    The reinforcing effects of addictive drugs are thought to be more robust when the onset of the drug's effects is fast. It is unclear whether this concept extends to intravenous self-administration (IVSA) of nicotine. We therefore sought to examine the effects of infusion duration on nicotine IVSA in rats. Male Lister hooded rats (n=8) were given daily 1 h limited access to fixed ratio-3 nicotine IVSA (0.03 mg/kg/infusion). Once nicotine IVSA was established, the effect of infusion duration on nicotine seeking was evaluated at a constant unit dose and volume (0.5, 5.0, and 19.6 s compared with the 1-s training infusion duration). Active responses were significantly reduced when the infusion duration was increased (i.e. 5 or 19.6 s compared with 0.5 and 1 s), and the effect was qualitatively similar to saline substitution. The likelihood of maintaining a reliable IVSA in rats was reduced by increasing the infusion duration. The infusion duration therefore represents an important determinant of nicotine reinforcement in rats. PMID:23907378

  1. Comparison of intravenous buprenorphine and methadone self-administration by recently detoxified heroin-dependent individuals.

    PubMed

    Comer, Sandra D; Sullivan, Maria A; Walker, Ellen A

    2005-12-01

    Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2, and 8 mg) and methadone (5, 10, and 20 mg). Participants (n = 6) were detoxified from heroin during the first 1 to 2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including "good drug effect", "high", and "liking" dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects. PMID:16144974

  2. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

    PubMed Central

    Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.

    2016-01-01

    Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392

  3. Zanamivir pharmacokinetics and pulmonary penetration into epithelial lining fluid following intravenous or oral inhaled administration to healthy adult subjects.

    PubMed

    Shelton, Mark J; Lovern, Mark; Ng-Cashin, Judith; Jones, Lori; Gould, Elizabeth; Gauvin, Jennifer; Rodvold, Keith A

    2011-11-01

    Zanamivir serum and pulmonary pharmacokinetics were characterized following intravenous (i.v.) or oral inhaled administration. I.v. zanamivir was given as intermittent doses of 100 mg, 200 mg, and 600 mg every 12 h (q12h) for two doses or as a continuous infusion (6-mg loading dose followed by 3 mg/h for 12 h). Oral inhaled zanamivir (two 5-mg inhalations q12h for two doses) was evaluated as well. Each zanamivir regimen was administered to six healthy subjects with serial pharmacokinetic sampling. In addition, a single bronchoalveolar lavage (BAL) fluid sample was collected at various time points and used to calculate epithelial lining fluid (ELF) drug concentrations for each subject. For intermittent i.v. administration of 100 mg, 200 mg, and 600 mg zanamivir, the median zanamivir concentrations in ELF collected 12 h after dosing were 74, 146, and 419 ng/ml, respectively, each higher than the historic mean 50% inhibitory concentrations for the neuraminidases of wild-type strains of influenza A and B viruses. Median ELF/serum zanamivir concentration ratios ranged from 55 to 79% for intermittent i.v. administration (when sampled 12 h after the last dose) and 43 to 45% for continuous infusion (when sampled 6 to 12 h after the start of the infusion). For oral inhaled zanamivir, the median zanamivir concentrations in ELF were 891 ng/ml for the first BAL fluid collection and 326 ng/ml for subsequent BAL fluid collections (when sampled 12 h after the last dose); corresponding serum drug concentrations were undetectable. This study demonstrates zanamivir's penetration into the human pulmonary compartment and supports the doses selected for the continuing development of i.v. zanamivir in clinical studies of influenza. PMID:21896909

  4. Zanamivir Pharmacokinetics and Pulmonary Penetration into Epithelial Lining Fluid following Intravenous or Oral Inhaled Administration to Healthy Adult Subjects▿

    PubMed Central

    Shelton, Mark J.; Lovern, Mark; Ng-Cashin, Judith; Jones, Lori; Gould, Elizabeth; Gauvin, Jennifer; Rodvold, Keith A.

    2011-01-01

    Zanamivir serum and pulmonary pharmacokinetics were characterized following intravenous (i.v.) or oral inhaled administration. I.v. zanamivir was given as intermittent doses of 100 mg, 200 mg, and 600 mg every 12 h (q12h) for two doses or as a continuous infusion (6-mg loading dose followed by 3 mg/h for 12 h). Oral inhaled zanamivir (two 5-mg inhalations q12h for two doses) was evaluated as well. Each zanamivir regimen was administered to six healthy subjects with serial pharmacokinetic sampling. In addition, a single bronchoalveolar lavage (BAL) fluid sample was collected at various time points and used to calculate epithelial lining fluid (ELF) drug concentrations for each subject. For intermittent i.v. administration of 100 mg, 200 mg, and 600 mg zanamivir, the median zanamivir concentrations in ELF collected 12 h after dosing were 74, 146, and 419 ng/ml, respectively, each higher than the historic mean 50% inhibitory concentrations for the neuraminidases of wild-type strains of influenza A and B viruses. Median ELF/serum zanamivir concentration ratios ranged from 55 to 79% for intermittent i.v. administration (when sampled 12 h after the last dose) and 43 to 45% for continuous infusion (when sampled 6 to 12 h after the start of the infusion). For oral inhaled zanamivir, the median zanamivir concentrations in ELF were 891 ng/ml for the first BAL fluid collection and 326 ng/ml for subsequent BAL fluid collections (when sampled 12 h after the last dose); corresponding serum drug concentrations were undetectable. This study demonstrates zanamivir's penetration into the human pulmonary compartment and supports the doses selected for the continuing development of i.v. zanamivir in clinical studies of influenza. PMID:21896909

  5. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    PubMed

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A

    2015-05-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation. PMID:25600245

  6. Intravenous Administration of Human ES-derived Neural Precursor Cells Attenuates Cuprizone-induced CNS Demyelination

    PubMed Central

    Crocker, Stephen J.; Bajpai, Ruchi; Moore, Craig S.; Frausto, Ricardo F.; Brown, Graham D.; Pagarigan, Roberto R.; Whitton, J. Lindsay; Terskikh, Alexey V.

    2011-01-01

    Aims Previous studies have demonstrated the therapeutic potential for human embryonic stem cell-derived neural precursor cells (hES-NPCs) in autoimmune and genetic animal models of demyelinating diseases. Herein, we tested whether intravenous (i.v) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. Methods C57Bl/6 mice were fed cuprizone (0.2%) for two weeks and then separated into two groups that either received an i.v. injection of hES-NPCs or i.v. administration of media without these cells. After an additional two weeks of dietary cuprizone treatment, CNS tissues were analyzed for detection of transplanted cells and differences in myelination in the region of the corpus callosum (CC). Results Cuprizone-induced demyelination in the CC was significantly reduced in mice treated with hES-NPCs compared with cuprizone-treated controls that did not receive stem cells. hES-NPCs were identified within the brain tissues of treated mice and revealed migration of transplanted cells into the CNS. A limited number of human cells were found to express the mature oligodendrocyte marker, O1, or the astrocyte marker, GFAP. Reduced apoptosis and attenuated microglial and astrocytic responses were also observed in the CC of hES-NPC-treated mice. Conclusions These findings indicated that systemically-administered hES-NPCs migrated from circulation into a demyelinated lesion within the CNS and effectively reduced demyelination. Observed reductions in astrocyte and microglial responses, and (c) the benefit of hES-NPC treatment in this model of myelin injury was not obviously accountable to tissue replacement by exogenously administered cells. PMID:21276029

  7. Repopulation of murine Kupffer cells after intravenous administration of liposome-encapsulated dichloromethylene diphosphonate.

    PubMed Central

    Yamamoto, T.; Naito, M.; Moriyama, H.; Umezu, H.; Matsuo, H.; Kiwada, H.; Arakawa, M.

    1996-01-01

    Kupffer cells were selectively eliminated in mice by the intravenous administration of liposome-entrapped dichloromethylene diphosphonate. At 5 days, small peroxidase-negative and acid-phosphatase-weakly-positive macrophages appeared, increased in number, and differentiated into peroxidase- and acid-phosphatase-positive Kupffer cells. Repopulating small macrophages actively proliferated, and the number of Kupffer cells returned to the normal level by day 14. The numbers of macrophage precursors in the liver as detected by the monoclonal antibodies ER-MP20 and ER-MP58 increased after liposome-entrapped dichloromethylene diphosphonate injection. ER-MP58-positive cells proliferated and differentiated into ER-MP20-positive cells and eventually into BM8-positive Kupffer cells in the liver. Bone-marrow-derived ER-MP58-positive cells were also detectable in the liver and differentiated into ER-MP20-positive cells, but they did not become BM8-positive macrophages. Macrophage colony-stimulating factor mRNA expression was enhanced in the liver 1 day after injection. The administration of macrophage colony-stimulating factor did not shorten the period of Kupffer cell depletion but increased the number and the proliferative capacity of repopulating Kupffer cells. These findings implied that repopulating Kupffer cells are derived from a macrophage precursor pool in the liver rather than from bone-marrow-derived monocytes. Local production of macrophage colony-stimulating factor in the liver plays a crucial role in the differentiation, maturation, and proliferation of Kupffer cells. Images Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 Figure 9 Figure 11 Figure 13 Figure 12 Figure 18 PMID:8863675

  8. Intravenous self-administration of mephedrone, methylone and MDMA in female rats

    PubMed Central

    Creehan, Kevin M.; Vandewater, Sophia A.; Taffe, Michael A.

    2015-01-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants (“bath salts”) mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation. PMID:25600245

  9. False positive in the intravenous drug self-administration test in C57BL/6J mice.

    PubMed

    Thomsen, Morgane; Caine, S Barak

    2011-06-01

    The objective of this study was to examine C57BL/6J (B6) mice during extinction conditions, after food training, and for rates and patterns of operant behavior that seems similar to behavior maintained by intravenous cocaine injections. The rationale was to evaluate the potential for false positives in the intravenous self-administration test using protocols common in studies of knockout mice backcrossed to B6. An additional aim was to assess the influence of food-associated and drug-associated cues and mouse strain. Mice were allowed to acquire lever pressing reinforced by sweetened condensed milk under a fixed ratio 1 then fixed ratio 2 schedule of reinforcement accompanied by a flashing light. A catheter base was then implanted for simulation of intravenous self-administration conditions. Mice were allowed to lever press with cues remaining the same as during food training but without further scheduled consequences (i.e. no drug or food reinforcers delivered). All mice sustained lever pressing for several weeks, and over half met commonly used criteria for 'self-administration behavior.' Thus, B6 mice showed perseveration of a previously reinforced behavior that closely resembled rates and patterns of drug self-administration. This effect in B6 mice was greater than with A/J mice, and the lack of extinction was even more robust in the presence of cocaine-associated cues than with food-associated cues. We suggest that a necessary criterion for positive results in the intravenous drug self-administration test include an increase in responding when cocaine is made available after extinction with saline self-administration. PMID:21522054

  10. Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the Failure Mode and Effects Analysis approach

    PubMed Central

    Ponzetti, Clemente; Canciani, Monica; Farina, Massimo; Era, Sara; Walzer, Stefan

    2016-01-01

    Background In oncology, an important parameter of safety is the potential treatment error in hospitals. The analyzed hypothesis is that of subcutaneous therapies would provide a superior safety benefit over intravenous therapies through fixed-dose administrations, when analyzed with trastuzumab and rituximab. Methods For the calculation of risk levels, the Failure Mode and Effect Analysis approach was applied. Within this approach, the critical treatment path is followed and risk classification for each individual step is estimated. For oncology and hematology administration, 35 different risk steps were assessed. The study was executed in 17 hematology and 16 breast cancer centers in Italy. As intravenous and subcutaneous were the only injection routes in medical available for trastuzumab and rituximab in oncology at the time of the study, these two therapies were chosen. Results When the risk classes were calculated, eight high-risk areas were identified for the administration of an intravenous therapy in hematology or oncology; 13 areas would be defined as having a median-risk classification and 14 areas as having a low-risk classification (total risk areas: n=35). When the new subcutaneous formulation would be applied, 23 different risk levels could be completely eliminated (65% reduction). Important high-risk classes such as dose calculation, preparation and package labeling, preparation of the access to the vein, pump infusion preparation, and infusion monitoring were included in the eliminations. The overall risk level for the intravenous administration was estimated to be 756 (ex-ante) and could be reduced by 70% (ex-post). The potential harm compensation for errors related to pharmacy would be decreased from eight risk classes to only three risk classes. Conclusion The subcutaneous administration of trastuzumab (breast cancer) and rituximab (hematology) might lower the risk of administration and treatment errors for patients and could hence indirectly have

  11. Speciation of arsenic in urine following intravenous administration of arsthinol in mice.

    PubMed

    Ajana, Imane; Astier, Alain; Gibaud, Stéphane

    2010-09-01

    Recent investigations have shown that arsthinol, a trivalent organoarsenic compound (dithiarsolane), has been active in vitro on leukemia cell lines and offers a better therapeutic index than arsenic trioxide, as estimated by the ratio LD50/IC50. To complete our understanding of its urinary excretion, a sensitive method using liquid chromatography coupled with mass spectrometry (LC-MS) was used. Mice were injected intravenously with a single dose of arsthinol at 0.2 mmol/kg of body weight. The amount of total arsenic in tissues and body fluids was determined by a colorimetric method and urine metabolites were analyzed on a C18 Acclaim PepMap 100 A column by LC-MS. Our results showed that only three arsenic species (acetarsol, acetarsol oxide and arsthinol) were detected in the first 24-h urine. Overall, this study confirms that the hydrolysis of dithiarsolanes to arsenoxides (i.e. acetarsol oxide) can be followed by an oxidation in arsonic acids (i.e. acetarsol). All these compounds are excreted in the urine. PMID:21495268

  12. Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion.

    PubMed Central

    De Wit, S; Hermans, P; Sommereijns, B; O'Doherty, E; Westenborghs, R; van de Velde, V; Cauwenbergh, G F; Clumeck, N

    1992-01-01

    The pharmacokinetics of oral administration of R 82913, or tetrahydroimidazol [4,5,1-jk]-benzodiazepin-2(1H)-one or -thione (TIBO), was compared with those of intravenous administration in five AIDS patients. TIBO was administered as a single daily 1-h infusion of 100 mg for 29 days and orally as a single daily dose for 14 days with three consecutive regimens of 100, 200, and 100 mg with probenecid (1 g) daily. Each cycle was followed by a wash-out period. Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid. Trough levels obtained with oral administration systematically remained far below the 90% inhibitory concentration of TIBO against human immunodeficiency virus type 1 (HIV-1). Tolerance of TIBO was excellent. No clinical efficacy could be demonstrated. p24 antigenemia decreased significantly in one patient under intravenous therapy. TIBO derivatives are promising anti-HIV-1 agents in vitro, but improvement of oral bioavailability is needed before implementation of long-term efficacy and tolerability studies. Moreover, rapid emergence of resistance, which has been recently documented, constitutes a major problem with most nonnucleoside reverse transcriptase inhibitors. PMID:1482134

  13. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    PubMed

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg. PMID:25283522

  14. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin after intravenous and intramuscular administration in beagle dogs.

    PubMed

    Yohannes, Sileshi; Awji, Elias Gebru; Lee, Seung-Jin; Park, Seung-Chun

    2015-03-01

    1.The aim of the present study was to determine the PKs of marbofloxacin in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration, the ex vivo and in vitro PK/PD indices of marbofloxacin against clinical isolates of Staphylococcus pseudintermedius, and the ex vivo AUC/MIC ratios associated with different levels of antibacterial activity. 2.After i.v. of marbofloxacin (2 mg/kg), the mean ± SEM values of AUC, t1/2β, Vss, and CL were 8.47 ± 3.51 h µg/mL, 8.08 ± 6.25 h, 2.32 ± 1.00 L/kg and 0.23 ± 0.06 L/kg/h and corresponding values after intramuscular injection were 11.37 ± 3.07 h µg/mL, 7.51 ± 3.70, 1.80 ± 0.90 L/kg and 0.17 ± 0.04 L/kg/h. After i.m. administration, a Cmax of 1.76 ± 0.09 µg/mL was achieved at Tmax of 0.47 ± 0.08 h. The ex-vivo AUC/MIC ratios required to produce bacteriostasis, bactericidal action and elimination of S. pseudintermedius were 65.03, 97.02 and 136.84 h. 3.The in vivo AUC/MIC ratios obtained after i.v. and i.m. administration of 2 mg/kg marbofloxacin (67.76 ± 1.23 and 91.18 ± 2.61) were below the ex vivo AUC/MIC ratios required for bactericidal activity and bacterial elimination (97.02 ± 9.24 2 mg/kg and 136.21 ± 7.58), suggesting that the recommended daily dosage (2 mg/kg) may not suffice to kill and eradicate S. pseudintermedius strains encountered in clinical area. PMID:25470431

  15. Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats.

    PubMed

    Jeong, Dong Won; Kim, Young Hoon; Kim, Hui Hyun; Ji, Hye Young; Yoo, Sun Dong; Choi, Won Rack; Lee, Soo Min; Han, Chang-Kyun; Lee, Hye Suk

    2007-03-01

    The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6-33.0 ml/min/kg), Vss (437-583 ml/kg), dose-normalized AUC (16.0-17.9 microg min/ml based on 1 mg/kg) and t1/2 (41.9-52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, Tmax, t1/2, dose-normalized Cmax (66-74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4-5.9 microg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance. PMID:17163409

  16. Intravenous self-administration of entactogen-class stimulants in male rats.

    PubMed

    Vandewater, Sophia A; Creehan, Kevin M; Taffe, Michael A

    2015-12-01

    The intravenous self-administration (IVSA) of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in rats, with up to half of subjects failing to acquire reliable drug intake. It is unknown if this changes under long-access conditions (6 h sessions) under which the IVSA of cocaine and methamphetamine escalates. The entactogen class cathinone stimulants which exhibit MDMA-like monoamine effects in the nucleus accumbens, mephedrone (4-methylmethcathinone) and methylone (3,4-methylenedioxymethcathinone), may support more reliable IVSA but results have been mixed. This study was designed to directly compare the IVSA of these three compounds. Groups of male Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and Progressive Ratio (PR; 0.125, 1.0 mg/kg/inf) dose-substitution procedures. Long access conditions escalated MDMA intake over the 6 h session but not in the first 2 h. In short access, drug intake was significantly higher in mephedrone-trained rats compared with either the methylone-trained or MDMA-trained groups during acquisition. Mephedrone resulted in the highest intakes during FR and PR dose-substitution in MDMA- and mephedrone-trained groups. Overall it was found that mephedrone is a more effective reinforcer than methylone or MDMA and represents a higher risk for compulsive use. PMID:26302654

  17. Degradation of zinc metallothionein after intravenous zinc administration in chicken liver and pancreas

    SciTech Connect

    Chang, C.H.; McCormick, C.C. )

    1991-03-15

    Previous results from the authors' laboratory have indicated that metallothionein (MT) mRNA levels following oral or parenteral zinc do not correspond to the accumulation of protein in liver and pancreas. Since the degradation of MT may influence the ultimate accumulation of MT in various tissues, the present study was conducted to investigate the rate of zinc MT degradation in liver and pancreas. Four-week-old male chicks were given intravenous zinc injections as zinc acetate. At various times, liver and pancreas were excised and homogenized. The cytosolic zinc MT was determined by gel filtration chromatography. To confirm relative tissue differences in the concentration of MT, G-75 fractions containing zinc MT from liver and pancreas cytosol were concentrated by ultrafiltration. Equal amounts of concentrate were subjected to PAGE and silver stain enhancement analysis. The results of PAGE verified that indeed the pancreas possesses over 2x higher MT than liver. Zinc MT degradation analysis was conducted beginning 24 hours following zinc administration. Since MT mRNA levels were minimal in both tissues after this time, changes in the concentration of MT were considered to reflect primarily degradation. The half-life of zinc MT for pancreas and liver was calculated to be 3.2 days and 2.0 days, respectively. Degradation rates of zinc MT in liver and pancreas were 0.0149 {plus minus} .005 h{sup {minus}1} and 0.0085 {plus minus} .004 h{sup {minus}1}, respectively. These data suggest that the rate of degradation of zinc MT in liver and pancreas accounts, in part, for the observed differences in MT concentration.

  18. Association of novelty-related behaviors and intravenous cocaine self-administration in Diversity Outbred mice

    PubMed Central

    Dickson, Price E.; Ndukum, Juliet; Wilcox, Troy; Clark, James; Roy, Brittany; Zhang, Lifeng; Li, Yun; Lin, Da-Ting; Chesler, Elissa J.

    2016-01-01

    Rationale Preference for and reaction to novelty are strongly associated with addiction to cocaine and other drugs. However, the genetic variants and molecular mechanisms underlying these phenomena remain largely unknown. Although the relationship between novelty- and addiction-related traits has been observed in rats, studies in mice have failed to demonstrate this association. New, genetically diverse, high-precision mouse populations including Diversity Outbred (DO) mice provide an opportunity to assess an expanded range of behavioral variation enabling detection of associations of novelty- and addiction-related traits in mice. Methods To examine the relationship between novelty- and addiction-related traits, male and female DO mice were tested on open field exploration, hole board exploration, and novelty preference followed by intravenous cocaine self-administration (IVSA; ten 2-hour sessions of fixed-ratio 1 and one 6-hour session of progressive ratio). Results We observed high variation of cocaine IVSA in DO mice with 43% reaching and 57% not reaching conventional acquisition criteria. As a group, mice that did not reach these criteria still demonstrated significant lever discrimination. Mice experiencing catheter occlusion or other technical issues (n = 17) were excluded from analysis. Novelty-related behaviors were positively associated with cocaine IVSA. Multivariate analysis of associations among novelty- and addiction-related traits revealed a large degree of shared variance (45%). Conclusions Covariation among cocaine IVSA and novelty-related phenotypes in DO mice indicates that this relationship is amenable to genetic dissection. The high genetic precision and phenotypic diversity in the DO may facilitate discovery of previously undetectable mechanisms underlying predisposition to develop addiction disorders. PMID:25238945

  19. Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration.

    PubMed

    Huang, Rongqin; Ke, Weilun; Han, Liang; Li, Jianfeng; Liu, Shuhuan; Jiang, Chen

    2011-03-01

    Gene therapy offers great potential for brain glioma. However, therapeutic genes could not reach glioma spontaneously. A glioma-targeting gene delivery system is highly desired to transfer exogenous genes throughout the tumor focus. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the main vector. Chlorotoxin (CTX), which has been demonstrated to bind specifically to receptor expressed in glioma, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-CTX. The cellular uptake of CTX itself was observed apparently in C6 glioma cells, almost not in 293 cells. The modification of CTX could significantly increase the cellular uptake of vectors and the DNA-loaded nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM-PEG-CTX/DNA NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM-PEG/DNA NPs. Furthermore, the gene expression of PAMAM-PEG-CTX/DNA NPs was higher and broader in glioma than that of unmodified and PEG-modified counterparts. The TUNEL analysis showed a more wide-extended apoptosis in the CTX-modified group, compared to other groups including commercial temozolomide group. The median survival time of CTX-modified group and temozolomide group was 59.5 and 49 days, respectively, significantly longer than that of other groups. The results suggested that CTX could be exploited as a special glioma-targeting ligand, and PAMAM-PEG-CTX/DNA NPs is a potential non-viral delivery system for gene therapy of glioma via intravenous administration. PMID:21185076

  20. Severe and prolonged hypophosphatemia after intravenous iron administration in a malnourished patient.

    PubMed

    Fierz, Y C; Kenmeni, R; Gonthier, A; Lier, F; Pralong, F; Coti Bertrand, P

    2014-04-01

    Malnutrition may result in a phosphate-deficient state owing to a chronically insufficient phosphate intake. Concomitant iron deficiency is common and often supplemented by the intravenous route. It is not widely recognized that some parenteral iron formulations can induce hypophosphatemia. Herein we report a case of a severe and symptomatic hypophosphatemia (0.18 mM, normal range 0.8-1.4 mM) associated with an inappropriately reduced tubular reabsorption of phosphate (33%, norm >95%) in a malnourished patient with anorexia/bulimia who received 2 × 500 mg iron carboxymaltose (FCM) intravenously. Despite intravenous and oral phosphate supplements, it required 2 months to achieve a normal serum phosphate level. Our case demonstrates that in a chronically malnourished and phosphate-deficient state intravenous FCM could potentially be dangerous. If this form of iron application cannot be avoided, phosphate supplementation before and after iron infusion as well as close monitoring of phosphate levels are needed. PMID:24569537

  1. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    PubMed Central

    Sun, Seung-Ho; Park, Sunju; Jeong, Jong-Jin; Lee, Kwang-Ho; Yu, Jun-Sang; Seo, Hyung-Sik; Kwon, Ki-Rok

    2015-01-01

    Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg. PMID:26120487

  2. Pharmacokinetic behavior of meloxicam in loggerhead sea turtles (Caretta caretta) after intramuscular and intravenous administration.

    PubMed

    Lai, Olimpia R; Di Bello, Antonio; Soloperto, Simona; Freggi, Daniela; Marzano, Giacomo; Cavaliere, Leonardo; Crescenzo, Giuseppe

    2015-04-01

    Data on reptile analgesia are scarce for nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids and almost completely lacking in sea turtles, even though emergencies requiring correct pain management are very frequent in their rehabilitative medicine; therefore, dosage regimens extrapolated from other species involve the risk of clinical failure and damage to the animals. We describe the pharmacokinetic behavior of meloxicam in the loggerhead sea turtle (Caretta caretta). We chose meloxicam because of its selective anti-cyclooxygenase-2 activity and lesser adverse side effects. No data are available on the capacity of turtles to tolerate NSAIDs, so we chose a dose of 0.1 mg/kg of meloxicam. Plasma concentrations of meloxicam were unexpectedly low both for intravenous (IV; maximum concentration [C(max)] = 0.04±0.02 µg/mL) and intramuscular (IM; C(max) = 0.07±0.09 µg/mL) administration. A double-peak phenomenon occurred after both IV (time for second peak concentration T(max2) = 10.33±10.89 h) and IM (T(max2) = 1.17±0.75 h). The second peak after IM injection was premature, so some difficulty and delay in absorption appears to be an appropriate explanation. Furthermore, the area under the curve, and therefore systemic bioavailability (F = 31.82±28.24%), after both IV (0.30±0.29) and IM (0.10±0.03) injection appeared particularly limited. Terminal elimination slope and mean residence time indicated fast elimination after IM dosing; as a consequence, plasma concentrations dropped below analytic limits in 8 h. Considering that IM is the favored route of administration of drugs in rescue centers, it is unlikely that meloxicam at 0.1 mg/kg is an appropriate choice, particularly in long-term pain management protocols. PMID:25647596

  3. Single Intravenous-dose Toxicity of Water-soluble Carthami-flos Pharmacopuncture (WCF) in Rats

    PubMed Central

    Jung, Da-jung; Choi, Yoo-min; Kim, Seok-hee; Kim, Jong-uk; Yook, Tae-han

    2014-01-01

    Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Water-soluble Carthami-flos pharmacopuncture (WCF) when used as a single intravenous-dose in 6-week-old, male and female Sprague-Dawley rats. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. 20 female and 20 male Spague-Dawley rats were divided into 4 groups of 5 female and 5 male animals per group. The rats in the three experimental groups received single intravenous injections with 0.125-mL, 0.25-mL and 0.5-mL/animal doses of WCF, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intravenous injection with a 0.5-mL dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, no significant changes in body weight, hematological parameters or clinical chemistry test results between the control group and the experimental groups were observed. Visual inspection after necropsy showed no abnormalities. Histopathological tests on the injected parts showed no significant differences, except for Group 1 females; however, the result was spontaneous generation and had no toxicological meaning because it was not dose-dependent. Therefore, this study showed that WCF had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single intravenous-dose tests of the test substance WCF in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, WCF is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed. PMID:25780707

  4. A single-puncture arthrocentesis technique, using a peripheral intravenous catheter.

    PubMed

    Skármeta, N P; Pesce, M C; Espinoza-Mellado, P A

    2016-09-01

    Arthrocentesis is a technique used for lavage of the inflammatory content of the supradiscal space and lysis of the fibrous strands attaching the articular disc to the superior compartment of the temporomandibular joint (TMJ). The most widely accepted and classical manner in which this technique is performed is through two-needle access to the superior joint space. Nevertheless, it has been reported in the literature that this technique is challenging and has several limitations. Thus, the use of a single-puncture approach has been proposed, which represents a less traumatic and easier to perform technique. The single-puncture approach may have several advantages over the classical two-needle approach in regard to completion time, tolerability, stabilization of the needle, and retention of the intra-articular medication. A single-puncture technique is described herein, which uses an intravenous catheter to provide simultaneous inflow/outflow for low or high volume irrigation of the TMJ. The feasibility and low cost of this technique are primary advantages; peripheral intravenous catheters are one of the most widely used devices for vascular access in the primary and hospital healthcare settings. PMID:27157632

  5. [Iron substitution in outpatients in Switzerland: Increase of costs associated with intravenous administration].

    PubMed

    Giger, Max; Achermann, Rita

    2013-01-01

    Iron anaemia and iron-deficient erythropoiesis are treated with oral iron supplements. For chronic haemodialysis or in the case of therapy failure or intolerance to oral iron therapy, intravenous supplements are administered. The costs of iron supplements borne by statutory health care insurance had strongly increased during the observation period from 2006 to 2010. Based on the invoice data of a large health insurance company with a market share of around 18 %, prescription data of iron preparations and laboratory tests were analysed and extrapolated to the Swiss population. During the 5-year observation period, costs of intravenous iron substitution increased by 16.5 m EUR (340.3 %) and the number of individuals treated by 243.5 %. A sharp rise was observed in women of menstruating age, which was mainly due to prescriptions issued by primary care physicians. More than 8 % of intravenous iron substitutions were administered without prior laboratory analysis,and must therefore be regarded as off-label use. A cost-benefit analysis is needed to demonstrate the additional value of intravenous over oral iron supplementation, and intravenous iron supplementation should be administered only to patients with proven iron deficiency. PMID:23916272

  6. Does a single dose of intravenous nicardipine or nimodipine affect the bispectral index following rapid sequence intubation?

    PubMed Central

    Lee, Jeong Jin; Ahn, Hyun Joo; Kim, Jin-Kyoung; Yang, Mikyung; Choi, Soo Joo; Kim, Hyun-Soo; Yang, Soo Hyun

    2010-01-01

    Background Theoretically, L-type calcium channel blockers could modulate anesthetic effects. Nicardipine does not affect the bispectral index (BIS), but nimodipine, which can penetrate the blood-brain barrier, has not been studied. The aim of this study was to evaluate whether a single dose of intravenous nicardipine or nimodipine could affect BIS following rapid sequence intubation. Methods This study was done in a double-blind, randomized fashion. Anesthesia was induced with fentanyl 2 µg/kg, thiopental sodium 5 mg/kg, and 100% oxygen. After loss of consciousness, patients received rocuronium 1.0 mg/kg and either a bolus of 20 µg/kg nicardipine, nimodipine, or a comparable volume of normal saline (n = 20). Intubation was performed 1 min after study drug administration. BIS, mean blood pressure (MBP), and heart rate (HR) were measured before anesthetic induction, after loss of consciousness, before intubation, during intubation, and 1, 2 and 5 min after intubation. Results BIS dropped rapidly after induction but increased to 60 before intubation in all groups irrespective of study drug. In nimodipine, the increase in BIS during intubation was not significant compared to pre-intubation, in contrast to the other two groups, but there was no difference in BIS during intubation. HR significantly increased, but MBP just rose to pre-induction values after intubation in nicardipine and nimodipine groups. BIS, MBP, and HR following intubation increased in control group. Conclusions A single dose of intravenous nicardipine or nimodipine could attenuate blood pressure increases but not affect BIS increases in rapid sequence intubation. PMID:21057615

  7. Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

    SciTech Connect

    Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T. )

    1991-03-01

    The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

  8. Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration

    SciTech Connect

    Garner, C.E. . E-mail: cegarner@rti.org; Sumner, S.C.J.; Davis, J.G.; Burgess, J.P.; Yueh, Y.; Demeter, J.; Zhan, Q.; Valentine, J.; Jeffcoat, A.R.; Burka, L.T.; Mathews, J.M.

    2006-08-15

    Workplace exposure to 1-bromopropane (1-BrP) can potentially occur during its use in spray adhesives, fats, waxes, and resins. 1-BrP may be used to replace ozone depleting solvents, resulting in an increase in its annual production in the US, which currently exceeds 1 million pounds. The potential for human exposure to 1-BrP and the reports of adverse effects associated with potential occupational exposure to high levels of 1-BrP have increased the need for the development of biomarkers of exposure and an improved understanding of 1-BrP metabolism and disposition. In this study, the factors influencing the disposition and biotransformation of 1-BrP were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). [1,2,3-{sup 13}C]1-BrP and [1-{sup 14}C]1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO{sub 2}, urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or {sup 14}CO{sub 2} (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid ({approx} 50%) and high ({approx} 71%) dose groups; while the percentage of the dose exhaled as {sup 14}CO{sub 2} decreased (19 to 10%). The molar ratio of exhaled {sup 14}CO{sub 2} to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. [{sup 14}C]1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (< 2%), or retained in the tissues and carcass (< 6%) of rats and mice administered i.v. 5 to 100 mg/kg [{sup 14

  9. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    PubMed

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. PMID:26096889

  10. A double-suicide autopsy case of potassium poisoning by intravenous administration of potassium aspartate after intake of some psychopharmaceuticals.

    PubMed

    Watanabe, K; Hasegawa, K; Suzuki, O

    2011-07-01

    We report a curious double-suicide autopsy case of both male and female who died of potassium poisoning by intravenous administration of concentrated potassium aspartate solution. The plasma concentrations of potassium of the male and female subjects were as high as 49.7 and 62.8 mEq/L, respectively. In addition to the high concentrations of potassium, toxic levels of phenobarbital, promethazine and chlorpromazine, and relatively low levels of etizolam and brotizolam were also detected from whole blood and urine specimens of both cadavers. Twenty empty plastic bottles (10-mL capacity) labeled 'ASPARA® Potassium Injection 10 mEq' were found at the suicide spot. To our knowledge, this is the first description for suicidal death by potassium aspartate; in all of the previous literature, they used potassium chloride intravenously or per os. PMID:20670988

  11. Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

    PubMed Central

    Lo, Chun-Min; Xu, Min; Yang, Qing; Zheng, Shuqin; Carey, Katherine M.; Tubb, Matthew R.; Davidson, W. Sean; Liu, Min; Woods, Stephen C.; Tso, Patrick

    2009-01-01

    CCK and apolipoprotein AIV (apo AIV) are gastrointestinal satiety signals whose synthesis and secretion by the gut are stimulated by fat absorption. Intraperitoneally administered CCK-8 is more potent in suppressing food intake than a similar dose administered intravenously, but the reason for this disparity is unclear. In contrast, both intravenous and intraperitoneally administered apo AIV are equally as potent in inhibiting food intake. When we compared the lymphatic concentration of CCK-8 and apo AIV, we found that neither intraperitoneally nor intravenously administered CCK-8 or apo AIV altered lymphatic flow rate. Interestingly, intraperitoneal administration of CCK-8 produced a significantly higher lymphatic concentration at 15 min than did intravenous administration. Intraperitoneal injection of apo AIV also yielded a higher lymphatic concentration at 30 min than did intravenous administration. Intraperitoneal administration of CCK-8 and apo AIV also resulted in a much longer period of elevated CCK-8 and apo AIV peptide concentration in lymph than intravenous administration. Furthermore, enzymatic activity of dipeptidyl peptidase IV (DPPIV) and aminopeptidase was higher in plasma than in lymph during fasting, and so, satiation peptides, such as CCK-8 and apo AIV in the lymph, are protected from degradation by the significantly lower DPPIV and aminopeptidase activity levels in lymph than in plasma. Therefore, the higher potency of intraperitoneally administered CCK-8 compared with intravenously administered CCK-8 in inhibiting food intake may be explained by both its higher concentration in lymph and the prolonged duration of its presence in the lamina propria. PMID:19020287

  12. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis.

    PubMed

    Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro

    2016-01-01

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain. PMID:27188335

  13. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis

    PubMed Central

    Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro

    2016-01-01

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain. PMID:27188335

  14. Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis) after intravenous and oral administration.

    PubMed

    Chang, Zhi-Qiang; Li, Zhao-Xin; Li, Jing-Bao; Wang, Ying-Zi; Li, Jian

    2014-08-01

    The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in flatfish tongue soles in the present study. After a single injection of SMM (40 mg/kg BW) to caudal vein of tongue sole at 20 °C, plasma drug concentration versus time data were best fitted to a three-compartment model, characterized with 0.2, 5.7, and 80.4 h for the half-life (t 1/2) of fast distribution, slow distribution, and elimination, respectively. The apparent volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg. After oral administration of SMM (200 mg/kg BW) to tongue soles at 20 °C, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t 1/2ka) and elimination (t 1/2β ) were 1.7 and 95.7 h, respectively. The maximal absorption concentration (C max) was estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5 % in tongue soles after oral administration. PMID:24577641

  15. N-acetylaspartylglutamate (NAAG) inhibits intravenous cocaine self-administration and cocaine-enhanced brain-stimulation reward in rats.

    PubMed

    Xi, Zheng-Xiong; Kiyatkin, Michael; Li, Xia; Peng, Xiao-Qing; Wiggins, Armina; Spiller, Krista; Li, Jie; Gardner, Eliot L

    2010-01-01

    Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural rewards (food, sucrose). In the present study, we investigated whether elevation of brain N-acetylaspartylglutamate (NAAG), an endogenous group II mGlu receptor agonist, by the NAAG peptidase inhibitor 2-PMPA attenuates cocaine's rewarding effects, as assessed by intravenous cocaine self-administration and intracranial electrical brain-stimulation reward (BSR) in rats. Systemic administration of 2-PMPA (10, 30, 100 mg/kg, i.p.) or intranasal administration of NAAG (100, 300 microg/10 microl/nostril) significantly inhibited intravenous cocaine self-administration under progressive-ratio (PR), but not under fixed-ratio 2 (FR2), reinforcement conditions. In addition, 2-PMPA (1, 10, 30 mg/kg, i.p) or NAAG (50, 100 microg/10 microl/nostril) significantly inhibited cocaine-enhanced BSR, but not basal BSR. Pretreatment with LY341495 (1 mg/kg, i.p.), a selective mGlu2/3 receptor antagonist, prevented the inhibitory effects produced by 2-PMPA or NAAG in both the self-administration and BSR paradigms. In vivo microdialysis demonstrated that 2-PMPA (10, 30, 100 mg/kg) dose-dependently attenuated cocaine-enhanced extracellular dopamine (DA) in the nucleus accumbens (NAc). 2-PMPA alone inhibited basal NAc DA release, an effect that was prevented by LY341495. These findings suggest that systemic administration of 2-PMPA or intranasal administration of NAAG inhibits cocaine's rewarding efficacy and cocaine-enhanced NAc DA - likely by activation of presynaptic mGlu2/3 receptors in the NAc. These data suggest a potential utility for 2-PMPA or NAAG in the treatment of cocaine addiction. PMID:19559037

  16. Intravenous iron administration together with parenteral nutrition to very preterm Jehovah's Witness twins

    PubMed Central

    Poorisrisak, Porntiva; Schroeder, Allan Mikael; Greisen, Gorm; Zachariassen, Gitte

    2014-01-01

    Preterm twin sisters (monozygotic) were born at gestational age 27 weeks and 5 days with birth weights of 935 and 735 g. They were admitted to our neonatal intensive care unit for a period of 1 month. Their parents were Jehovah’s Witnesses and refused blood transfusion for their preterm daughters. Subcutaneous erythropoietin and intravenous iron were given as a prophylactic to avoid anaemia. PMID:24891477

  17. [The protective activity of 2 normal immunoglobulin preparations for intravenous administration in experimental Pseudomonas aeruginosa infection].

    PubMed

    Vasilev, Ch L; Veleva, K V; Tekelieva, R Kh; Pencheva, P I

    1991-02-01

    The antibody levels in 18 batches of the preparations of human immunoglobulin, Immunovenin and Immunovenin-Intact, for intravenous injection were determined in the enzyme immunoassay with the use of the mixture of P. aeruginosa lipopolysaccharide antigens of seven immunotypes. The average antibody titers in these preparations were identical. The preparations were found to have protective action against P. aeruginosa experimental infection in mice. PMID:1907793

  18. Perfusion thallium imaging of type I diabetes patients with end stage renal disease: Comparison of oral and intravenous dipyridamole administration

    SciTech Connect

    Boudreau, R.J.; Strony, J.T.; duCret, R.P.; Kuni, C.C.; Wang, Y.; Wilson, R.F.; Schwartz, J.S.; Castaneda-Zuniga, W.R. )

    1990-04-01

    Eighty patients with type I diabetes and end stage renal disease were prospectively evaluated for coronary artery disease with dipyridamole-thallium-201 scintigraphy and quantitative coronary angiography. Forty patients received dipyridamole orally, and 40 received it intravenously. The prevalence of coronary artery disease was 53%. There were no significant differences in the accuracy of the two dipyridamole tests (sensitivity = 85%, specificity = 85%, accuracy = 85% for the oral group; sensitivity = 86%, specificity = 72%, accuracy = 79% for the intravenous group). Combining the 80 patients into a single group gave a sensitivity of 86%, a specificity of 79%, and an accuracy of 83% for the detection of coronary disease. Although the accuracy of this test in this patient population was similar to that previously reported for other groups, the prevalence of disease was high and resulted in a low predictive value of a negative test (83%).

  19. Nalfurafine hydrochloride, a selective κ opioid receptor agonist, has no reinforcing effect on intravenous self-administration in rhesus monkeys.

    PubMed

    Nakao, Kaoru; Hirakata, Mikito; Miyamoto, Yohei; Kainoh, Mie; Wakasa, Yoshio; Yanagita, Tomoji

    2016-01-01

    Nalfurafine hydrochloride [(E)-N-[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl)-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion). These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm. PMID:26786553

  20. Use of High-Performance Liquid Chromatography To Study the Pharmacokinetics of Colistin Sulfate in Rats following Intravenous Administration

    PubMed Central

    Li, Jian; Milne, Robert W.; Nation, Roger L.; Turnidge, John D.; Smeaton, Timothy C.; Coulthard, Kingsley

    2003-01-01

    The pharmacokinetics of colistin was investigated using specific high-performance liquid chromatography (HPLC) to measure the concentrations of colistin and colistin A and B in plasma and urine in five rats after administration of an intravenous bolus of 1 mg of colistin sulfate/kg of body weight. There were differences in the pharmacokinetic behaviors of unbound colistin A and B. This is the first report of the use of HPLC to study the pharmacokinetics of colistin and its two major components. PMID:12709357

  1. Tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects: an open-label, randomized, single-center study.

    PubMed

    Liu, Yani; Zhou, Jiali; Li, Zhongfang; Yang, Chunxiao; Wu, Jianhong; Zhang, Yu; Shi, Shaojun; Li, Yunqiao

    2015-12-01

    The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300 mg/m(2) administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C max, AUC0-t, t 1/2, V d, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300 mg/m(2), the mean (standard deviation) pharmacokinetic parameters were as follows: C max = 5.18 (0.58), 47.80 (10.10), and 69.93 (9.72) µg/mL; AUC0-t = 25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µg h/mL; AUC0-∞ = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/mL; t 1/2 = 8.77 (2.57), 7.64 (1.81), and 9.08 (1.64) h; CL = 1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V d = 13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C max, AUC0-t, and AUC0-∞ increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue). PMID:25173761

  2. Anxiolytic-like actions of buspirone in a runway model of intravenous cocaine self-administration

    PubMed Central

    Ettenberg, Aaron; Bernardi, Rick E.

    2007-01-01

    In previous work from our laboratory, rats traversing a straight alley for a reward of IV cocaine have been observed to develop ambivalence about entering the goal box. Over trials, animals repeatedly run toward the goal box, stop at the entry point, and then retreat back toward the start box. This unique pattern of retreat behavior has been shown to reflect a form of “approach-avoidance conflict” that stems from the subjects' concurrent positive (cocaine reward) and negative (cocaine-induced anxiety) associations with the goal box. Buspirone, a partial 5-HT1A agonist, has been reported to produce anxiolytic-like actions in the clinic, but has had mixed results in experimental tests of anxiety using animal subjects. Since most animal tests of conflict/anxiety employ the administration of foot-shock – a relatively strong aversive stimulus – it was of interest to determine whether buspirone would alter the more subtle approach-avoidance conflict observed in well-trained animals running a straight alley for single daily injections of 1.0 mg/kg IV cocaine. Runway testing consisted of single daily trials that continued until consistent approach-avoidance retreats were exhibited. Each animal was then pretreated 30 min prior to runway testing with vehicle and one of three doses of buspirone (0.0, 1.0, 2.5 or 5.0 mg/kg IP). Testing continued in a counterbalanced manner until all rats had experienced each dose of buspirone with 3 days of cocaine-only trials between each test day. The number of retreats exhibited on each trial served as an index of the approach-avoidance conflict present on that trial. Results clearly demonstrated that buspirone (at the two higher doses) attenuated the retreat behavior of animals approaching a goal-box for IV cocaine – an action consistent with its anxiolytic-like actions in the clinic. PMID:17064759

  3. Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin β1 Augments Angiogenesis in Ischemic Legs.

    PubMed

    Goto, Kazuko; Takemura, Genzou; Takahashi, Tomoyuki; Okada, Hideshi; Kanamori, Hiromitsu; Kawamura, Itta; Watanabe, Takatomo; Morishita, Kentaro; Tsujimoto, Akiko; Miyazaki, Nagisa; Ushikoshi, Hiroaki; Kawasaki, Masanori; Mikami, Atsushi; Kosai, Ken-ichiro; Minatoguchi, Shinya

    2016-02-01

    When injected directly into ischemic tissue in patients with peripheral artery disease, the reparative capacity of endothelial progenitor cells (EPCs) appears to be limited by their poor survival. We, therefore, attempted to improve the survival of transplanted EPCs through intravenous injection and gene modification. We anticipated that overexpression of integrin β1 will enable injected EPCs to home to ischemic tissue, which abundantly express extracellular matrix proteins, the ligands for integrins. In addition, integrin β1 has an independent angiogenesis-stimulating function. Human endothelial colony-forming cells (ECFCs; late-outgrowth EPCs) were transduced using a lentiviral vector encoding integrin β1 (ITGB1) or enhanced green fluorescent protein (GFP). We then locally or systemically injected phosphate-buffered saline or the genetically modified ECFCs (GFP-ECFCs or ITGB1-ECFCs; 1 × 10(5) cells each) into NOD/Shi-scid, IL-2Rγnull mice whose right femoral arteries had been occluded 24 hours earlier. Upregulation of extracellular matrix proteins, including fibronectin, was apparent in the ischemic legs. Four weeks later, blood perfusion of the ischemic limb was significantly augmented only in the ITGB1-ECFC group. Scanning electron microscopy of vascular casts revealed increases in the perfused blood vessels in the ischemic legs of mice in the ITGB1-ECFC group and significant increases in the density of both capillaries and arterioles. Transplanted ECFC-derived vessels accounted for 28% ± 4.2% of the vessels in the ITGB1-ECFC group, with no cell fusion. Intravenous administration of ECFCs engineered to home to ischemic tissue appears to efficiently mediate therapeutic angiogenesis in a mouse model of peripheral artery disease. Significance: The intravenous administration of endothelial colony-forming cells (ECFCs) genetically modified to overexpress integrin β1 effectively stimulated angiogenesis in ischemic mouse hindlimbs. Transplanted ECFCs were

  4. Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.

    PubMed

    Wang, Haiquan; Liao, Zhengbu; Sun, Xiaochuan; Shi, Quanhong; Huo, Gang; Xie, Yanfeng; Tang, Xiaolan; Zhi, Xinggang; Tang, Zhaohua

    2014-11-01

    Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials. PMID:24973706

  5. Biological disposition of sodium dichloroacetate in animals and humans after intravenous administration.

    PubMed

    Lukas, G; Vyas, K H; Brindle, S D; Le Sher, A R; Wagner, W E

    1980-04-01

    Sodium dichloroacetate, a potential antidote for lactic acidosis, was administered intravenously to rats, dogs, and four humans. In three rats, maximum plasma sodium dichloroacetate concentrations were 120-164 microgram/ml after a 100-mg/kg dose and declined with half-lives of 2.1-4.4 hr. In two dogs, maximal concentrations of 447 and 508 microgram/ml were attained after a 100-mg/kg dose. The subsequent decline was relatively slow with approximate half-lives of 17.1 and 24.6 hr. An intravenous infusion of 10 mg/kg was administered over 20 min to two human subjects. Two other subjects received 20 mg/kg. After the infusion, maximum plasma concentrations of 19.9 and 24.7 microgram/ml were seen with the lower dose and 57.3 and 74.9 microgram/ml were achieved with the higher dose. Thereafter, concentrations declined rapidly with half-lives of 20-36 min. The observed large interspecies differences in half-lives could be explained in terms of differences in the apparent volume of distribution and/or clearance. PMID:7373538

  6. Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

    PubMed Central

    Morar-Mitrica, Sorina; Puri, Manasi; Beumer Sassi, Alexandra; Fuller, Joshua; Hu, Ping; Crotts, George; Nesta, Douglas

    2015-01-01

    The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions. PMID:26073995

  7. Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents.

    PubMed

    Rocha, Luis B; Schaberle, Fábio; Dąbrowski, Janusz M; Simões, Sérgio; Arnaut, Luis G

    2015-01-01

    We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm² led to the complete tumour regression in 83% of the mice. PMID:26670231

  8. Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

    PubMed Central

    Rocha, Luis B.; Schaberle, Fábio; Dąbrowski, Janusz M.; Simões, Sérgio; Arnaut, Luis G.

    2015-01-01

    We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. PMID:26670231

  9. The effect of intravenous administration of variable-dose flumazenil after fixed-dose ketamine and midazolam in healthy cats.

    PubMed

    Ilkiw, J E; Farver, T B; Suter, C; McNeal, D; Steffey, E P

    2002-06-01

    The effects of intravenous administration of variable-dose flumazenil (0, 0.001, 0.005, 0.01, and 0.1 mg/kg) after ketamine (3 mg/kg) and midazolam (0.0 and 0.5 mg/kg) were studied in 18 healthy unmedicated cats from time of administration until full recovery. End-points were chosen to determine whether flumazenil shortened the recovery period and/or modified behaviors previously identified and attributed to midazolam. Overall, flumazenil administration had little effect on recovery or behaviors. One minute after flumazenil administration, all cats were recumbent but a greater proportion of cats which received the highest dose assumed sternal recumbency with head up than any other group. Although not significant, those cats that received the highest flumazenil dose also had shorter mean times for each of the initial recovery stages (lateral recumbency with head up, sternal recumbency with head up and walking with ataxia) than any of the other treatment groups that received midazolam. For complete recovery, flumazenil did decrease the proportion of the cats that was sedated, but did not shorten the time to walking without ataxia. Based on this study, the administration of flumazenil in veterinary practice, at the doses studied, to shorten and/or improve the recovery from ketamine and midazolam in healthy cats cannot be recommended. PMID:12081613

  10. Acute pulmonary pathology and sudden death in rats following the intravenous administration of the plasticizer, DI (2-ethylhexyl) phthalate, solubilized with Tween surfactants. [pathology of vinyl plastics poisoning

    NASA Technical Reports Server (NTRS)

    Schulz, C. O.; Rubin, R. J.; Hutchins, G. M.

    1975-01-01

    Intravenous administration of 200-300 mg/kg of di(2-ethylhexyl)phthalate (DEHP) solubilized in aqueous solutions of several Tween surfactants caused respiratory distress in rats. There was a dose-dependent lethality with death generally occurring within 90 minutes after injection. The lungs from DEHP:Tween treated animals were enlarged, generally darkened, and in some cases showed hemorrhagic congestion. Neither the overt symptoms nor the morphologic alterations resulting from DEHP:Tween administration could be reproduced by intravenous administration of aqueous Tween solutions alone. The absence of pulmonary abnormalities following the intravenous administration of DEHP as an aqueous emulsion given either alone or even as soon as 2 minutes after pretreatment with Tween 80, suggests that the specific in vivo interaction between DEHP and Tween surfactants depends on the prior formation of water-soluble micelles of DEHP.

  11. Therapeutic Benefit of Intravenous Administration of Human Umbilical Cord Blood- Mononuclear Cells Following Intracerebral Hemorrhage in Rat

    PubMed Central

    Seghatoleslam, Masoumeh; Jalali, Mehdi; Nikravesh, Mohammad Reza; Hosseini, Mahmoud; Hamidi Alamdari, Daryoush; Fazel, Alireza

    2012-01-01

    Objective(s) Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell–based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we hypothesize transplanted HUCB derived mononuclear cells (UC-MCs) can decrease injured volume and also ameliorate neurological function in ICH rats. Materials and Methods Experimental ICH was induced by intrastriatal administration of collagenase in rats. One day after surgery, the rats were divided into 3 groups to receive intravenously either BrdU positive human UC-MCs [(4×106 and 8×106 cells in 1 ml saline, n=10 respectively) as treated groups] or the same amount of saline [as lesion group (n=10)]. There was also one group (control) that received only vehicle solution of collagenase. The animals were evaluated for 14 days with behavioral tests. Transplanted UC-MCs were detected by immunohistochemistry. Histological data and scores of functional tests were analyzed using ANOVA. Cellular co-localization of BrdU+ cells in the histological slides was determined by software Image J. Results Intravenously transplanted UC-MCs migrated selectively to the hematomal area and reduce injured volume. The UC-MCs transplanted groups showed better performance on functional tests after 2 weeks compared with the lesion and control groups (P< 0.05). There was no difference in the functional recovery and injured volume improvement between the 2 treated groups. Conclusion Intravenously transplanted UC-MCs accelerate neurological function recovery of ICH rat and diminish the striatum lesion size. Thus these cells may provide a potential cell candidate for cell-based therapy in ICH. PMID:23492836

  12. Pharmacokinetics of dexamethasone following intra-articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone.

    PubMed

    Soma, L R; Uboh, C E; Liu, Y; Li, X; Robinson, M A; Boston, R C; Colahan, P T

    2013-04-01

    This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO. PMID:22632064

  13. Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado-Joseph disease neurological phenotype.

    PubMed

    Conceição, Mariana; Mendonça, Liliana; Nóbrega, Clévio; Gomes, Célia; Costa, Pedro; Hirai, Hirokazu; Moreira, João Nuno; Lima, Maria C; Manjunath, N; Pereira de Almeida, Luís

    2016-03-01

    Others and we showed that RNA interference holds great promise for the treatment of dominantly inherited neurodegenerative disorders such as Machado-Joseph disease (MJD), for which there is no available treatment. However, successful experiments involved intracranial administration of viral vectors and there is a need for a safer and less invasive procedure. In this work, we successfully generated stable nucleic acid lipid particles (SNALPs), incorporating a short peptide derived from rabies virus glycoprotein (RVG-9r) and encapsulating small interfering RNAs (siRNAs), which can target mutant ataxin-3. The developed formulation exhibited important features that make it adequate for systemic administration: high encapsulation efficiency of siRNAs, ability to protect the encapsulated siRNAs, appropriate and homogeneous particle size distribution. Following optimization of the formulation and in vitro validation of its efficacy to silence the MJD-causing protein - mutant ataxin-3 - in neuronal cells, in vivo experiments showed that intravenous administration of RVG-9r-targeted SNALPs efficiently silenced mutant ataxin-3 reducing neuropathology and motor behavior deficits in two mouse models of MJD. To our knowledge, this is the first report showing beneficial impact of a non-viral gene silencing strategy in MJD and the first time that a non-invasive systemic administration proved to be beneficial on a polyglutamine disorder. Our study opens new avenues towards MJD therapy that can also be applied to other neurodegenerative diseases linked to the production of pathogenic proteins. PMID:26757259

  14. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    PubMed Central

    Peplow, Philip V.

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints. PMID:26487831

  15. Thallium-201 myocardial imaging after pharmacologic coronary vasodilation: Preliminary results of a comparison between oral and intravenous administration of dipyridamole

    SciTech Connect

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Lemire, F.; Leveille, J.

    1985-05-01

    Although the diagnostic utility of Tl-201 myocardial imaging after dipyridamole (DIP) infusion is well established, the intravenous form of the drug is not commercially available. The author prospectively studied 34 consecutive patients referred for coronary angiography. With in a 2 week period, each patient underwent cardiac catheterization and Tl-201 myocardial imaging following both oral and i.v. DIP. With the patient supine, DIP was infused at a rate of 0.56 mg/kg over 4 minutes. Tl-201 was injected 3 min. after the end of the infusion with the patient standing. Myocardial imaging was performed in 3 views at 3 min. and 4 hrs after Tl-201 injection. All patients were then randomized to either 200 mg or 400 mg of oral DIP. Imaging protocol was similar to the i.v. technique, except for a delay of 45-60 min. before Tl-201 injection. Myocardial regional perfusion was evaluated by 2 independent observers using original analog and background substracted digital images with segmental profile analysis. For the 17 patients who recieved DIP 400 mg, the sensitivity was 75%(9/12) with the infusion and 83% (10/12) with the oral dose. Side effects were minor and less frequent with the oral DIP. Despite the small number of patients studied, Tl-201 imaging following 400 mg oral DIP administration proved to be reliable alternative to the intravenously induced coronary vasodilation.

  16. Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats.

    PubMed

    Vishkautsan, Polina; Papich, Mark G; Thompson, George R; Sykes, Jane E

    2016-09-01

    OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range. ANIMALS 6 healthy cats. PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15. RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation. CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects. PMID:27580104

  17. Biliary excretion of radioactivity after intravenous administration of (3H)25-hydroxyvitamin D3 in man

    SciTech Connect

    Ledger, J.E.; Watson, G.J.; Compston, J.E.

    1986-04-01

    The biliary excretion of radioactivity after intravenous (3H)25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than (3H)25-hydroxyvitamin D3. No free (3H)25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following (3H)25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.

  18. Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil.

    PubMed

    Fukuta, Tatsuya; Asai, Tomohiro; Sato, Akihiko; Namba, Mio; Yanagida, Yosuke; Kikuchi, Takashi; Koide, Hiroyuki; Shimizu, Kosuke; Oku, Naoto

    2016-06-15

    Fasudil, a Rho-kinase inhibitor, is a promising neuroprotectant against ischemic stroke; however, its low bioavailability is an obstacle to be overcome. Our previous study revealed that the liposomal drug delivery system is a hopeful strategy to increase the therapeutic efficacy of neuroprotectants. In the present study, the usefulness of intravenously administered liposomal fasudil for cerebral ischemia/reperfusion (I/R) injury treatment was examined in transient middle cerebral artery occlusion (t-MCAO) rats. The results showed that PEGylated liposomes of approximately 100nm in diameter accumulated more extensively in the I/R region compared with those of over 200nm. Confocal images showed that fluorescence-labeled liposomal fasudil was widely distributed in the I/R region, and was not noticeably taken up by microglia, which are well-known resident macrophages in the brain, and neuronal cells. These data indicated that liposomal fasudil mainly exerted its pharmacological activity by releasing fasudil from the liposomes in the I/R region. Moreover, liposomal fasudil effectively suppressed neutrophil invasion and brain cell damage in the t-MCAO rats, resulting in amelioration of their motor function deficits. These findings demonstrated both the importance of particle size for neuroprotectant delivery and the effectiveness of liposomal fasudil for the treatment of cerebral I/R injury. PMID:27107903

  19. Pharmacokinetics of (-)-folinic acid after oral and intravenous administration of the racemate.

    PubMed Central

    Greiner, P O; Zittoun, J; Marquet, J; Cheron, J M

    1989-01-01

    1. A pharmacokinetic study of the natural (-)-isomer of folinic acid ((-)-5 CHOTHF) and of total (-)-folates was performed in 12 healthy subjects after i.v. and oral administration of the racemic form of folinic acid. 2. After a 25 mg i.v. injection, (-)-5 CHOTHF kinetics were described by a biexponential function. The mean steady state volume of distribution (Vss) was 161; systemic and renal clearances averaged 335 and 53 ml min-1, respectively. After the same oral dose, (-)-5 CHOTHF was rapidly absorbed. Plasma concentrations of unchanged drug were much lower than those achieved after i.v. administration but in nine subjects, the disposition kinetics were also biexponential. Absolute bioavailability was only 4% as a consequence of a significant intestinal first pass effect. 3. AUC and t1/2Z values for total (-)-folates were similar after both routes of administration, indicating that the drug was fully absorbed. However the AUC of the active metabolite after i.v. dosage was only half that after oral dosage. 4. The amounts of total (-)-folates excreted in urine after both routes of administration were not significantly different and averaged one third of the dose after 24 h, whereas excretion of (-)-5 CHOTHF was three times less after oral treatment than after parenteral treatment. 5. Oral administration is a more suitable route for folinic acid therapy because more of the active metabolite is produced than after parenteral injection. PMID:2789922

  20. A case of anorexia nervosa with Marchiafava-Bignami Disease that responded to high-dose intravenous corticosteroid administration.

    PubMed

    Tao, Hiroki; Kitagawa, Nobuki; Kako, Yuki; Yamanaka, Hiroyoshi; Ito, Koichi; Denda, Kenzo; Koyama, Tsukasa

    2007-11-15

    We report the first known case of anorexia nervosa (AN) with Marchiafava-Bignami Disease (MBD) that responded to high-dose intravenous corticosteroid administration. A 16-year-old Japanese female with AN was diagnosed with MBD after rapid weight loss. During the acute stage, she suffered from a sudden onset of coma. After regaining consciousness, she presented with lack of movement, apathy, labile affect, and poverty of speech. On admission, magnetic resonance imaging showed an area of demyelination in the splenium of the corpus callosum. Positron emission tomography obtained 7 days after admission showed areas of hypoperfusion in the medial temporal lobe and in regions anterior and posterior to the central sulcus. PMID:17933499

  1. Pharmacokinetics of buprenorphine hydrochloride following intramuscular and intravenous administration to American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Gustavsen, Kate A.; Guzman, David Sanchez-Migallon; Knych, Heather K.; Petritz, Olivia A.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

    2014-01-01

    Conclusions and Clinical Relevance—Buprenorphine was rapidly absorbed, and bioavailability was good after IM administration to American kestrels. Plasma buprenorphine concentrations were > 1 ng/mL for 9 hours after both IM and IV administration. These results, in combination with those of a pharmacodynamic study, suggested that the analgesic effects of buprenorphine could last at least 6 to 9 hours in this species. Further investigations of the duration of analgesic effects, multiple-dose protocols, and potential adverse effects of buprenorphine are warranted in American kestrels and other raptors.

  2. Breath /sup 14/CO2 after intravenous administration of (/sup 14/C)aminopyrine in liver diseases

    SciTech Connect

    Pauwels, S.; Geubel, A.P.; Dive, C.; Beckers, C.

    1982-01-01

    The determination of of /sup 14/CO2 in breath after oral administration of (/sup 14/C)aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the (/sup 14/C)aminopyrine breath test (ABT) was performed after intravenous administration of (/sup 14/C)aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86 +/- 0.1% (mean +/- SD) in controls and significantly less in patients (0.46 +/- 0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16 +/- 0.13%), alcoholic cirrhosis (0.2 +/ 0.15%0, and untreated postnecrotic cirrhosis (0.47 +/- 0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86 +/- 0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83 +/- 0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test.

  3. Scintigraphic tracking of mesenchymal stem cells after portal, systemic intravenous and splenic administration in healthy beagle dogs.

    PubMed

    Spriet, Mathieu; Hunt, Geraldine B; Walker, Naomi J; Borjesson, Dori L

    2015-01-01

    Mesenchymal stem cells have been proposed to treat liver disease in the dog. The objective of this study was to compare portal, systemic intravenous and splenic injections for administration of mesenchymal stem cells to target the liver in healthy beagle dogs. Four healthy beagle dogs were included in the study. Each dog received mesenchymal stem cells via all three delivery methods in randomized order, 1 week apart. Ten million fat-derived allogeneic mesenchymal stem cells labeled with Technetium-99m (99mTc)-hexamethyl-propylene amine oxime(HMPAO) were used for each injection. Right lateral, left lateral, ventral, and dorsal scintigraphic images were obtained with a gamma camera equipped with a low-energy all-purpose collimator immediately after injection and 1, 6, and 24 h later. Mesenchymal stem cells distribution was assessed subjectively using all four views. Pulmonary, hepatic, and splenic uptake was quantified from the right lateral view, at each time point. Portal injection resulted in diffuse homogeneous high uptake through the liver, whereas the systemic intravenous injection led to mesenchymal stem cell trapping in the lungs. After splenic injection, mild splenic retention and high homogeneous diffuse hepatic uptake were observed. Systemic injection of mesenchymal stem cells may not be a desirable technique for liver therapy due to pulmonary trapping. Splenic injection represents a good alternative to portal injection. Scintigraphic tracking with 99mTc-HMPAO is a valuable technique for assessing mesenchymal stem cells distribution and quantification shortly after administration. Data obtained at 24 h should be interpreted cautiously due to suboptimal labeling persistence. PMID:25582730

  4. Biocompatibility evaluation of pH and glutathione-responsive nanohydrogels after intravenous administration.

    PubMed

    Pérez, Elena; Olmo, Rosa; Teijón, César; Muñíz, Enriqueta; Montero, Nuria; Teijón, Jose M; Blanco, M Dolores

    2015-12-01

    Nanotoxicology has emerged as an important subdiscipline of nanotechnology due to the new healthy risks associated with the use of nanosystems for therapy and diagnostic. The biocompatibility of four stimuli-responsive nanohydrogel (NG) formulations based on different proportions of N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and 2-acrylamidoethyl carbamate (2AAECM), and cross-linked with N,N-cystaminebisacrylamide (CBA) or N-methylenebisacrylamide (NMBA) has been evaluated after intravenous injection in Wistar rats. All nanohydrogels were pH-sensitive, and those with CBA were also glutathione-responsive. Haematological and coagulation parameters revealed most nanogel formulations did not cause modification, only the NHA 80/15/5-CBA formulation induced a transitory light increase in platelets. Prothrombin time was in the reference normal range, there were no modifications of fibrinogen concentration and an increase in antithrombin III was observed on the last day of the study. Blood biochemical parameters such as AST, ALT, ALP, BUN, and creatinine were in the standard range for rats. The activity of enzyme antioxidant defences (SOD, CAT and GSSG-R) and total glutathione were evaluated in liver, kidney and spleen samples. Nanohydrogels cross-linked with the disulphide reducible CBA-cross-linker caused a decrease in GSSG/GSH content and an increase in GSSG-R activity in the spleen. The antioxidant response is also reflected by modifications of SOD activity in liver and kidney of NHA 80/15/5-CBA and NHA 80/10/10-NMBA groups. Histology showed no tissue damage, inflammation or morphological change in liver, kidney and spleen. Overall, the results demonstrated modifications of antioxidant defences; however, no acute or very significant changes in biomarkers of liver or kidney damage were observed. PMID:26402420

  5. Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration

    PubMed Central

    Legette, LeeCole; Ma, Lian; Reed, Ralph L.; Miranda, Cristobal L.; Christensen, J. Mark; Rodriguez-Proteau, Rosita; Stevens, Jan F.

    2012-01-01

    Scope Xanthohumol (XN), a dietary flavonoid found in hops, may have health protective actions against cardiovascular disease and type 2 diabetes. Yet, there are limited data on the pharmacokinetics (PK) of XN. This study provides PK parameters for XN and its major metabolites in rats. Methods and results A pharmacokinetic study was conducted in male jugular vein-cannulated Sprague-Dawley rats. Rats (n=12/group) received an intravenous (IV) injection (1.86 mg/kg BW) or an oral gavage of a low (1.86 mg/kg BW), medium (5.64 mg/kg BW), or high (16.9 mg/kg BW) dose of XN. Plasma samples were analyzed for XN and its metabolites using LC-MS/MS. The maximum concentration (Cmax) and area under the curve (AUC0-96 h) of total XN (free and conjugated) were 2.9 ± 0.1 mg/L and 2.5 ± 0.3 h*mg/L in the IV group, 0.019 ± 0.002 mg/L and 0.84 ± 0.17 h*mg/L in the oral low group, 0.043 ± 0.002 mg/L and 1.03 ± 0.12 h*mg/L in the oral medium group, and 0.15 ± 0.01 mg/L and 2.49 ± 0.10 h*mg/L in the oral high group. Conclusion The bioavailability of XN is dose-dependent and approximately 0.33, 0.13 and 0.11 in rats, for the low, medium and high dose groups, respectively. PMID:22147307

  6. Antitumor Effect of Folate-Targeted Liposomal Doxorubicin in KB Tumor-Bearing Mice after Intravenous Administration

    PubMed Central

    Riviere, Kareen; Huang, Zhaohua; Jerger, Katherine; Macaraeg, Nichole; Szoka, Francis C.

    2010-01-01

    The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) over-expressing tumors in vitro, particularly in KB human carcinoma cells. However, there are few studies evaluating the in vivo efficacy of FTL-Dox in KB murine xenograft models. In this study, we investigated the antitumor activity of FTL-Dox injected intravenously in mice bearing KB tumors. Folate ligands comprising of folate-polyethyleneglycol-distearoylphosphatidylethanolamine (FA-PEG-DSPE) were synthesized with different MW PEG. To design an optimum FTL-Dox formulation for therapeutic studies, we prepared various FTLs and characterized their in vitro targeting and in vivo tissue biodistribution. Mice were administered a single intravenous injection of free Dox, non-targeted PEGylated liposomal Dox (PL-Dox), or FTL-Dox. FTLs and PLs accumulated similarly in tumor tissue, despite FTLs’ faster clearance from circulation. Mice treated with FTL-Dox 20 mg/kg had a slightly greater tumor growth inhibition and almost a 50% increase in life span than mice receiving PL-Dox 20 mg/kg (P = 0.0121; log-rank test). We conclude that FTLs administered systemically have the potential to enhance the delivery of anticancer drugs in vivo; however, their removal by FR expressing normal tissues may have to be blocked if the benefits of tumor targeting are to be realized. PMID:20353291

  7. Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature

    PubMed Central

    Eek, Daniel; Krohe, Meaghan; Mazar, Iyar; Horsfield, Alison; Pompilus, Farrah; Friebe, Rachel; Shields, Alan L

    2016-01-01

    Objective The emergence of various modes of administration for cancer treatment, including oral administration, brings into focus the importance of patient preference for administration. The purpose of this research was to evaluate the administration preferences of cancer patients, specifically between oral and intravenous (IV) treatment, as well as the factors contributing to preference. Methods A literature search was conducted in OvidSP to identify research in which the preferences of cancer patients for oral or IV treatment have been evaluated. Data were analyzed in two stages: 1) those articles that directly compared preference between modes of administration were tallied to determine explicit preference for oral or IV treatment; and 2) all attributes associated with patient preference were documented. Results Of the 48 abstracts identified as part of the initial OvidSP search, eight articles were selected for full-text review. One article was removed following full-text review, and seven additional articles were identified through a gray literature search, yielding a total of 14 articles for evaluation. In Stage 1, 13 of the 14 articles compared preference, of which eleven articles (84.6%) reported that patients preferred oral treatment over IV, while two (15.4%) stated that cancer patients preferred IV treatment over oral. In Stage 2, the most frequently reported attributes contributing to preference included convenience, ability to receive treatment at home, treatment schedule, and side effects. Discussion Evidence suggests that oncology patients prefer oral treatment to IV. Rationale for preference was due to a number of factors, including convenience, perception of efficacy, and past experience. Further evaluation should be conducted, given the limited data on patient preference in oncology. PMID:27601886

  8. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review

    PubMed Central

    Harel, Ziv; Kamel, Kamel S.

    2016-01-01

    Background and Objectives Hyperkalemia is a common electrolyte disorder that can result in fatal cardiac arrhythmias. Despite the importance of insulin as a lifesaving intervention in the treatment of hyperkalemia in an emergency setting, there is no consensus on the dose or the method (bolus or infusion) of its administration. Our aim was to review data in the literature to determine the optimal dose and route of administration of insulin in the management of emergency hyperkalemia. Design, Setting, Participants, & Measurements We searched several databases from their date of inception through February 2015 for eligible articles published in any language. We included any study that reported on the use of insulin in the management of hyperkalemia. Results We identified eleven studies. In seven studies, 10 units of regular insulin was administered (bolus in five studies, infusion in two studies), in one study 12 units of regular insulin was infused over 30 minutes, and in three studies 20 units of regular insulin was infused over 60 minutes. The majority of included studies were biased. There was no statistically significant difference in mean decrease in serum potassium (K+) concentration at 60 minutes between studies in which insulin was administered as an infusion of 20 units over 60 minutes and studies in which 10 units of insulin was administered as a bolus (0.79±0.25 mmol/L versus 0.78±0.25 mmol/L, P = 0.98) or studies in which 10 units of insulin was administered as an infusion (0.79±0.25 mmol/L versus 0.39±0.09 mmol/L, P = 0.1). Almost one fifth of the study population experienced an episode of hypoglycemia. Conclusion The limited data available in the literature shows no statistically significant difference between the different regimens of insulin used to acutely lower serum K+ concentration. Accordingly, 10 units of short acting insulin given intravenously may be used in cases of hyperkalemia. Alternatively, 20 units of short acting insulin may be

  9. Blood and liver acetaldehyde concentration in rats following acetaldehyde inhalation and intravenous and intragastric ethanol administration

    SciTech Connect

    Watanabe, A.; Hobara, N.; Nagashima, H.

    1986-10-01

    Ethanol is metabolized to acetaldehyde, a highly reactive product of ethanol oxidation. Ethanol might be blended with gasoline and used as a fuel in the future; biohazard of acetaldehyde inhalation must be discussed. Recent improvements in our ability to measure acetaldehyde levels in blood and various tissues have made the assessment of acetaldehyde's role in alcoholic organ intoxication possible. Blood and liver acetaldehyde concentrations in rats were reported as being linearly correlated following intragastric ethanol administration. Acetaldehyde was administered by inhalation to study its toxicity. However, liver concentrations following the inhalation was not investigated. The present communication describes the relationship between blood and liver acetaldehyde concentrations in rats following acetaldehyde inhalation and different routes of ethanol administration.

  10. Supplemental Intravenous Crystalloid Administration Does Not Reduce the Risk of Surgical Wound Infection

    PubMed Central

    Kabon, Barbara; Akça, Ozan; Taguchi, Akiko; Nagele, Angelika; Jebadurai, Ratnaraj; Arkilic, Cem F.; Sharma, Neeru; Ahluwalia, Arundhathi; Galandiuk, Susan; Fleshman, James; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Wound perfusion and oxygenation are important determinants of the development of postoperative wound infections. Supplemental fluid administration significantly increases tissue oxygenation in surrogate wounds in the subcutaneous tissue of the upper arm in perioperative surgical patients. We tested the hypothesis that supplemental fluid administration during and after elective colon resections decreases the incidence of postoperative wound infections. Patients undergoing open colon resection were randomly assigned to small (n=124, 8 mL·kg-1·h-1) or large volume (n=129, 16-18 mL·kg-1·h-1) fluid management. Our major outcomes were two distinct criteria for diagnosis of surgical wound infections: 1) purulent exudate combined with a culture positive for pathogenic bacteria and 2) Center for Disease Control criteria for diagnosis of surgical wound infections. All wound infections diagnosed using either criterion by a blinded observer in the 15 days following surgery were considered in the analysis. Wound healing was evaluated with the ASEPSIS scoring system. Of the patients given small fluid administration, 14 had surgical wound infections; 11 given large fluid therapy had infections, P=0.46. ASEPSIS wound healing scores were similar in both groups: 7±16 (small volume) vs. 8±14 (large volume), P=0.70. Our results suggest that supplemental hydration in the range tested does not impact wound infection rate. PMID:16244030

  11. Intravenous tryptophan administration attenuates cortisol secretion induced by intracerebroventricular injection of noradrenaline.

    PubMed

    Sutoh, Madoka; Kasuya, Etsuko; Yayou, Ken-ichi; Ohtani, Fumihiro; Kobayashi, Yosuke

    2016-02-01

    This study was conducted to investigate the possibility of suppression of stress-induced cortisol (CORT) secretion by tryptophan (TRP) administration and to better understand its regulatory mechanisms by using a noradrenaline (NA) injection into the third ventricle (3V) as a stress model in cattle. A total of 25 Holstein steers with a cannula in the 3V were used. First, the increase in CORT secretion was observed following a NA injection into the 3V in a dose-dependent manner, verifying the appropriateness of this treatment as a stress model of CORT secretion (Experiment 1). The effect of prior-administration of TRP into peripheral blood with a dose that has been demonstrated to increase brain 5-hydroxytryptamine levels on the elevation of plasma CORT induced by NA or corticotropin-releasing hormone (CRH) was then examined (Experiment 2). The prior administration of TRP suppressed NA-induced, but not CRH-induced, CORT elevation. These results suggest that an increase in TRP absorption into peripheral blood could suppress the stress-induced CORT secretion in cattle via the attenuation of the stimulatory effect of NA on the hypothalamic CRH release. PMID:26260296

  12. Oral Delivery of Therapeutic Proteins and Peptides: An Overview of Current Technologies and Recommendations for Bridging from Approved Intravenous or Subcutaneous Administration to Novel Oral Regimens.

    PubMed

    Philippart, M; Schmidt, J; Bittner, B

    2016-03-01

    Since the early 1980s, therapeutic proteins and peptides have become established as an important class of pharmaceuticals. Due to their low oral bioavailability, which results from pre-systemic degradation and poor gastrointestinal absorption, most therapeutic proteins and peptides are administered intravenously. While subcutaneous formulations of some therapeutic proteins and peptides have been shown to improve patient convenience and reduce medical resource utilization, oral administration is generally the preferred administration route. Some therapeutic proteins and peptides employing novel oral delivery technologies have reached late-stage clinical development. To develop a new oral formulation of a therapeutic protein or peptide currently marketed as an injectable product, technical, nonclinical, and clinical studies are required to demonstrate similar safety and efficacy compared with the existing administration route. Since there is little experience with oral therapeutic proteins and peptides, this review provides recommendations for bridging from an approved intravenous or subcutaneous regimen to novel oral administration of the same therapeutic protein or peptide, based on precedents from intravenous-to-subcutaneous bridging approaches for trastuzumab, rituximab, tocilizumab, and bortezomib. If the pharmacokinetic/pharmacodynamic relationship is well characterized, demonstration of comparability in prespecified pharmacokinetic parameters might form a basis for establishing similar efficacy and safety of the oral formulation vs. the reference product. Although oral administration of therapeutic proteins and peptides remains challenging, given recent progress with novel delivery technologies, intravenous/subcutaneous-to-oral nonclinical and clinical bridging programs may soon be utilized to support approval of new oral formulations. PMID:26536331

  13. Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation.

    PubMed

    Acosta, E P; Brundage, R C; King, J R; Sánchez, P J; Sood, S; Agrawal, V; Homans, J; Jacobs, R F; Lang, D; Romero, J R; Griffin, J; Cloud, G; Whitley, R; Kimberlin, D W

    2007-06-01

    Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates. PMID:17392728

  14. Cardiorespiratory effects of intravenous bolus administration and infusion of ketamine-midazolam in dogs.

    PubMed

    Jacobson, J D; Hartsfield, S M

    1993-10-01

    Twelve healthy dogs were used to determine the cardiorespiratory effects of i.v. administered ketamine (10 mg/kg of body weight) and midazolam (0.5 mg/kg). Half the dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and the other half received the K-M as an infusion over 15 minutes. Induction of anesthesia by use of K-M was good in all dogs. Ketamine-midazolam combination as a bolus or infusion induced minimal cardiorespiratory effects, except for significant (P < 0.05) increases in mean heart rate and rate-pressure product. The increase in heart rate was greater in dogs of the infusion group. Mild and transient respiratory depression was observed in dogs of both groups immediately after administration of K-M, but was greater in dogs of the bolus group than in dogs of the infusion group. Duration of action of K-M for chemical restraint was short. Salivation and defecation were observed in a few dogs. Extreme muscular tone developed in 1 dog after K-M bolus administration. PMID:8250397

  15. Effects of Oral and Intravenous Administration of Buspirone on Food–Cocaine Choice in Socially Housed Male Cynomolgus Monkeys

    PubMed Central

    Czoty, Paul W; Nader, Michael A

    2015-01-01

    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food–drug choice procedure in which a cocaine self-administration dose–effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations. PMID:25393717

  16. Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans

    PubMed Central

    Lofwall, M.R.; Nuzzo, P.A.; Campbell, C.; Walsh, S.L.

    2014-01-01

    Aripiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1a receptors and antagonist at 5-HT2 receptors. Because both dopamine and serotonin systems are involved in the action of cocaine, this study aimed to determine if aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole effects on ad lib cigarette smoking and a novel 40-hour cigarette smoking abstinence procedure. Healthy adults with regular cocaine and cigarette use completed this ~30-day inpatient double blind, randomized, placebo-controlled mixed-design study. An oral placebo lead-in period was followed by randomization to oral aripiprazole (0, 2 or 10 mg daily; n=7 completed/group). Three sets of test sessions, each consisting of three cocaine sample-choice (i.e., self-administration) sessions and one dose-response session, were conducted (during the lead-in period and after randomization before and after achieving aripiprazole steady state). Sample-choice sessions tested three cocaine doses (0, 20, and 40 mg/70 kg, i.v.) with one dose (random order) administered in each sample session; subjective, observer-rated and physiologic outcomes were collected repeatedly before and after cocaine administration. Later that day, participants chose between receiving the sample dose from that morning or descending amounts of money for seven trials ($19, 16, 13, 10, 7, 4, 1). Dose response sessions administered the three cocaine doses in ascending order for pharmacodynamic and potential pharmacokinetic assessment. A set of two cigarette smoking topography sessions were conducted during placebo lead-in and after randomization; one with and one without 40-hours of cigarette smoking abstinence. Number of ad lib cigarettes smoked during non-session days was also collected. Cocaine produced prototypic pharmacodynamic effects and self-administration; neither were significantly altered by aripiprazole. The 40-hour smoking abstinence procedure reliably produced nicotine

  17. Distribution of human umbilical cord blood-derived mesenchymal stem cells in the Alzheimer's disease transgenic mouse after a single intravenous injection.

    PubMed

    Park, Sang Eon; Lee, Na Kyung; Lee, Jeongmin; Hwang, Jung Won; Choi, Soo Jin; Hwang, Hyeri; Hyung, Brian; Chang, Jong Wook; Na, Duk L

    2016-03-01

    The aim of this study was to track the migration of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered through a single intravenous injection and to observe the consequential therapeutic effects in a transgenic Alzheimer's disease mouse model. Ten-month-old APP/PS1 mice received a total injection of 1×10 cells through the lateral tail vein and were killed 1, 4, and 7 days after administration. On the basis of immunohistochemical analysis, hUCB-MSCs were not detected in the brain at any of the time points. Instead, most of the injected mesenchymal stem cells were found to be distributed in the lung, heart, and liver. In terms of the molecular effects, statistically significant differences in the amyloid β protein, neprilysin, and SOX2 levels were not observed among the groups. On the basis of the results from this study, we suggest that single intravenously administered hUCB-MSCs are not delivered to the brain and also do not have a significant influence on Alzheimer's disease pathology. PMID:26752148

  18. Effects of Propofol and Midazolam on the Inflammation of Lungs after Intravenous Endotoxin Administration in Rats

    PubMed Central

    Celik, Mine Gursac; Saracoglu, Ayten; Saracoglu, Tolga; Kursad, Husnu; Dostbil, Aysenur; Aksoy, Mehmet; Ahiskalioglu, Ali; Ince, Ilker

    2015-01-01

    Objective: Pulmonary complications are important sepsis (such as ARDS, diffuse pneumonia). Acute respiratory distress syndrome (ARDS) is characterized by the extensive migration of neutrophils into alveoli of the lungs. Propofol and midazolam are the most widely used agents for sedation in intensive care units. Aimed to investigate the effects of anaesthesia with propofol and midazolam on measured hemodynamic variables and neutrophil migration induced by Escherichia Coli endotoxin (ECE) in pulmonary viscera. Materials and Methods: Forty Sprague Dawley male rats were randomly assigned to four groups: Thiopental Sodium 30 mg/kg was administered intraperitoneally to anesthetize the rats. They were ventilated via tracheotomy. Femoral artery was cannulated for the measurement of continuous blood pressure and gases. Group C was the control. After the administration of 1 mL/kg 0.9% NaCL, infusion began at 1 mL/kg/h rate. In Group E 15 mg/kg lipopolysaccharide derived from ECE was administered iv. In Group PE, after a bolus dose of 10 mg/kg propofol and 15 mg/kg ECE, 10 mg/kg/h infusion was applied. In Group ME, after 0.1 mg/kg midazolam bolus dose and 15 mg/kg ECE administration, 0.1 mg/kg/h infusion was administered iv. Rats were sacrified by iv potassium chloride. The lungs were then removed, fixed in 10% buffered formalin for 3 days and embedded in paraffin. They were graded on a scale of 0–3 according to the aggregation of neutrophils. Results: There was intense neutrophil migration in Group E (grade 2, 3). However, although mild neutrophil migration was obtained in 70% of the rat lungs in Group ME (grade 1, 2), it was recorded in only 30% of Group PE (grade 1). Conclusion: The sepsis model induced by ECE and compared with midazolam, propofol anaesthesia is associated with less neutrophil infiltration. In the light of the literature, propofol attenuate the free-radical-mediated lipid peroxidation and systemic inflammation in patients. PMID:26180495

  19. Screening and confirmatory analyses of flunixin in tissues and bodily fluids after intravenous or intramuscular administration to cull dairy cows with or without lipopolysaccharide challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty cull dairy cows (645 ± 83 kg) were treated with 2.2 mg/kg bw flunixin by intravenous (IV) or intramuscular (IM) administration with, or without, exposure to lipopolysaccharide in a two factor balanced design. The usefulness of screening assays to identify violative flunixin levels in a varie...

  20. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration

    PubMed Central

    Sattar, Adeel; Xie, Shuyu; Huang, Lingli; Iqbal, Zahid; Qu, Wei; Shabbir, Muhammad A.; Pan, Yuanhu; Hussain, Hafiz I.; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Iqbal, Mujahid; Yuan, Zonghui

    2016-01-01

    Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg−1 b.w.), IM (10 mg kg−1 b.w.), and IV (10 mg kg−1 b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL−1, 6.3 h × μg mL−1, and 6.66 h × μg mL−1, while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology. PMID:27536243

  1. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.

    PubMed

    Sattar, Adeel; Xie, Shuyu; Huang, Lingli; Iqbal, Zahid; Qu, Wei; Shabbir, Muhammad A; Pan, Yuanhu; Hussain, Hafiz I; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Iqbal, Mujahid; Yuan, Zonghui

    2016-01-01

    Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg(-1) b.w.), IM (10 mg kg(-1) b.w.), and IV (10 mg kg(-1) b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL(-1), 6.3 h × μg mL(-1), and 6.66 h × μg mL(-1), while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology. PMID:27536243

  2. Stability of morphine sulfate in infusion devices and containers for intravenous administration.

    PubMed

    Duafala, M E; Kleinberg, M L; Nacov, C; Flora, K P; Hines, J; Davis, K; McDaniel, A; Scott, D

    1990-01-01

    The stability of morphine sulfate in one brand of polyvinyl chloride (PVC) container, one brand of glass syringe, and two brands of disposable infusion devices was determined. Solutions of morphine sulfate 2 and 15 mg/mL were used to fill the PVC containers and drug administration devices. Stability was determined for both concentrations of morphine sulfate at room temperature (23-25 degrees C) and 4 degrees C in the PVC containers, glass syringes, and disposable infusion devices; stability was also determined at 31 degrees C in the disposable infusion devices. At 0, 1, 2, 4, 7, 12, and 15 days, portions of the solutions were removed and assayed in triplicate by a stability-indicating high-performance liquid chromatographic method. At each time point the drug-infusion fluid combinations were inspected visually for color changes and the presence of particulate matter, and pH was measured. Morphine sulfate 2 and 15 mg/mL remained stable for at least 12 days in all the containers and devices at each temperature tested. No substantial changes in the pH or physical appearance of the solutions were observed. Morphine sulfate can be repackaged in the disposable glass syringe, PVC container, and both disposable infusion devices for routine clinical use. PMID:2301422

  3. Bidirectional Tachycardia after an Acute Intravenous Administration of Digitalis for a Suicidal Gesture

    PubMed Central

    Sabatini, Diletta; Truscelli, Giovanni; Ciccaglioni, Antonio; Gaudio, Carlo

    2014-01-01

    Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined. PMID:25221680

  4. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    PubMed

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail. PMID:23772453

  5. The pharmacokinetics of the β2-adrenoceptor agonist, tulobuterol, in Beagle dogs following transdermal and intravenous administration.

    PubMed

    Kim, J H; Kim, T H; Park, H J; Choi, Y J; Kang, J H; Song, K H; Koo, T S; Seo, K W

    2016-02-01

    Tulobuterol is a β2-adrenergic agonist that was the first bronchodilator approved as a transdermal patch for humans. Previous studies have examined the pharmacokinetics of tulobuterol in humans but not in the veterinary species. In this study, the pharmacokinetics of tulobuterol was examined in healthy Beagle dogs after transdermal and intravenous administration. The Cmax was 2.09 ng/mL at 16.0 h for a 0.2 mg/kg patch and 4.85 ng/mL at 13.6 h for a 0.4 mg/kg patch. The effective blood level in humans is 1-3 ng/mL, a concentration achieved using the 0.2 mg/kg patch in dogs. In conclusion, application of a 0.2 mg/kg tulobuterol patch to healthy dogs led to an apparently effective blood concentration for 24 h. PMID:26639828

  6. Effects of a Selective Cannabinoid CB2 Agonist and Antagonist on Intravenous Nicotine Self Administration and Reinstatement of Nicotine Seeking

    PubMed Central

    Gamaleddin, Islam; Zvonok, Alexander; Makriyannis, Alexandros; Goldberg, Steven R.; Le Foll, Bernard

    2012-01-01

    Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2) have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio) and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg) and CB2 agonist AM1241 (1 to 10 mg/kg) on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior. PMID:22291896

  7. Pulmonary and Systemic Pharmacokinetics of Inhaled and Intravenous Colistin Methanesulfonate in Cystic Fibrosis Patients: Targeting Advantage of Inhalational Administration

    PubMed Central

    W. S. Yapa, Shalini; Li, Jian; Patel, Kashyap; Wilson, John W.; Dooley, Michael J.; George, Johnson; Clark, Denise; Poole, Susan; Williams, Elyssa; Porter, Christopher J. H.

    2014-01-01

    The purpose of this study was to define the pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at <1.0 mg/liter for 12 h postdose. Nebulization of CMS resulted in relatively high sputum concentrations of CMS and formed colistin compared to those resulting from i.v. administration. The systemic availability of CMS was low following nebulization of 2 and 4 million IU (7.93% ± 4.26% and 5.37% ± 1.36%, respectively), and the plasma colistin concentrations were below the limit of quantification. Less than 2 to 3% of the nebulized CMS dose was recovered in the urine samples in 24 h. The therapeutic availability and drug targeting index for CMS and colistin following inhalation compared to i.v. delivery were significantly greater than 1. Inhalation of CMS is an effective means of targeting CMS and formed colistin for delivery to the lungs, as high lung exposure and minimal systemic exposure were achieved in CF subjects. PMID:24550334

  8. Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach

    PubMed Central

    Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

    2015-01-01

    Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

  9. Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and Intravenous Administration of CMS in Critically Ill Patients

    PubMed Central

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Mimoz, Olivier

    2014-01-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. PMID:25267660

  10. Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

    PubMed

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

    2014-12-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. PMID:25267660

  11. [Sudden death following a single oral administration of haloperidol].

    PubMed

    Remijnse, P L; Eeckhout, A M; van Guldener, C

    2002-04-20

    A 39-year-old man was admitted with myasthenia, alcoholic hepatitis and electrolyte abnormalities due to an inadequate nutritional state. On admission the ECG showed a prolonged QTc interval (0.46 s). The patient was treated with intravenous fluid and supplementary vitamins and minerals. On the third day of admission the patient developed a delirium, partly due to alcohol withdrawal, and was therefore treated with oxazepam 50 mg 3 times daily and a single dose of haloperidol 5 mg. One hour after ingesting haloperidol, the patient suddenly succumbed and resuscitation was not successful. The autopsy revealed a cardiomyopathy but no explanation for the sudden death. Due to the temporal relationship between the ingestion of haloperidol and this sudden death, we assume that haloperidol induced a fatal arrhythmia in the presence of a preexisting prolonged repolarisation time. To the best of our knowledge, sudden death after a single oral therapeutic dose of haloperidol has not previously been described. PMID:11998355

  12. The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats.

    PubMed

    Ilkiw, J E; Suter, C M; McNeal, D; Farver, T B; Steffey, E P

    1996-06-01

    The effects of intravenous administration of variable-dose midazolam and ketamine (3 mg/kg) were studied in twelve healthy unmedicated cats from time of administration until full recovery. A range of midazolam doses (0.0, 0.05, 0.5, 1.0, 2.0 and 5.0 mg/kg) was chosen, so that beneficial and/or detrimental effects could be documented and the therapeutic window for further study determined. One minute after administration of ketamine, all cats had assumed a lateral position, mostly with head up. Muscle tone was increased (100%), apneustic breathing pattern evident in 92% of cats, chewing without stimulation of the oropharyngeal area was observed in most cats (97%), but most cats did not salivate (87%). At 2.5 min after completion of ketamine injection and 1 min after administration of saline, a similar picture was observed, except that salivation was evident. All cats chewed or swallowed in response to a finger or laryngoscope placed in the oropharyngeal area and, while most cats were not aware of a noxious stimulus to the tail, some cats were aware of a noxious stimulus to the paw. Recovery from ketamine alone was rapid and smooth with cats rolling into sternal recumbency and then cautiously walking with ataxia. Recovery to walking without incoordination was also rapid (< 2 h) and no abnormal behavioural patterns were observed during recovery. Administration of midazolam after ketamine, had beneficial effects and the therapeutic window for midazolam was found to lie between 0.05 mg/kg and 0.5 mg/kg. Administration of any dose of midazolam after ketamine caused a greater proportion of cats to assume a laterally recumbent position with head down compared with ketamine alone, however, the time period of recumbency was only significantly longer with a midazolam dose of 2.0 mg/kg or above. Doses of midazolam of 0.5 mg/kg or above decreased muscle rigidity but did not affect salivation or respiratory pattern observed in cats which received ketamine alone. A significantly

  13. Intravenous administration of alpha-1-proteinase inhibitor in patients of PiZ and PiM phenotype. Preliminary report

    SciTech Connect

    Moser, K.M.; Smith, R.M.; Spragg, R.G.; Tisi, G.M.

    1988-06-24

    Nine patients with moderate pulmonary emphysema, six of PiZ phenotype and three of PiM phenotype, have received a single intravenous infusion of alpha-1-proteinase inhibitor (human) (A1PI), in a dose of 60 mg/kg over a 30-minute period. They also received a tracer dose (300 microCi) of /sup 131/I-labeled A1PI. No active or passive immunization against hepatitis was given. No acute toxicity was observed. Compared with baseline data, significant elevations of serum A1PI (measured both antigenically and as anti-elastase activity) occurred, with a serum half-life approximating 110 hours. Bronchoalveolar lavage fluid, obtained 48 hours after infusion, reflected a significant increase in A1PI concentration versus baseline bronchoalveolar lavage fluid values. Serial gamma camera images of the lungs confirmed persistence of enhanced lung radioactivity for several days. Urinary desmosine excretion did not change following A1PI infusion. During the period of follow-up thus far, no patient has had chronic toxicity, results of liver function tests have been stable, and there has been no development of hepatitis B antigen or antibodies to hepatitis B surface or core antigens.

  14. Study of Intravenous Single-Dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Kwon, Ki-Rok; Yu, Jun-Sang; Sun, Seung-Ho; Lee, Kwang-Ho

    2016-01-01

    Objectives: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. Results: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. Conclusion: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal. PMID:27386149

  15. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    PubMed

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration. PMID:27305820

  16. Chronic variable stress and intravenous methamphetamine self-administration - Role of individual differences in behavioral and physiological reactivity to novelty.

    PubMed

    Taylor, S B; Watterson, L R; Kufahl, P R; Nemirovsky, N E; Tomek, S E; Conrad, C D; Olive, M F

    2016-09-01

    Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. PMID:27163191

  17. Complying with the Occupational Safety and Health Administration's Bloodborne Pathogens Standard: implementing needleless systems and intravenous safety devices.

    PubMed

    Marini, Michelle A; Giangregorio, Maeve; Kraskinski, Joanna C

    2004-03-01

    Preventing the transmission of bloodborne pathogens to healthcare workers has been a mission and a challenge of the healthcare industry for over 20 years. The development of the Occupational Safety and Health Administration Bloodborne Pathogens Standard in 1991 and the passing of the Needlestick Safety Act in 2000 mandated hospitals to develop an Exposure Control Plan to protect workers from these pathogens. Children's Hospital Boston began implementation of a needleless system in 1993. Employees readily accepted these systems into practice, because they were convenient and easy to use. A marked decrease in exposures to bloodborne pathogens naturally followed, which is consistent with the national data. The transition to intravenous (i.v.) safety devices at Children's Hospital began in 2000 and proved to be more of a challenge. First, the clinicians must choose a safety product, which requires developing and implementing a trial plan with potential catheters. This selection process is especially difficult in pediatrics where successful placement of the smallest-gauge catheter, no. 24, is imperative. After choosing an i.v. safety product, successful transition is dependent upon the thoroughness of i.v. safety device training and a commitment by the clinicians to the use of these products. Although the number of needlestick injuries and subsequent transmission of bloodborne pathogens have been further reduced with the use of i.v. safety devices, needlestick injuries still occur. This results from a lack of familiarity with the engineering of the device and therefore poor technique or a failure to activate the safety mechanism. Staff resistance due to loss of expertise with the new device and patient care concerns are additional barriers to the use of these new products. Addressing these obstacles and providing adequate training for all clinicians were required for successful implementation of these i.v. safety devices. PMID:15094584

  18. Increased intravenous morphine self-administration following Roux-en-Y gastric bypass in dietary obese rats.

    PubMed

    Biegler, Jessica M; Freet, Christopher S; Horvath, Nelli; Rogers, Ann M; Hajnal, Andras

    2016-05-01

    Roux-en-Y gastric bypass (RYGB) surgery is a commonly performed and very effective method to achieve significant, long-term weight loss. Opioid analgesics are primarily used to manage postoperative pain as fewer alternative medication options are available for bariatric surgery patients than for the general population. Recent clinical studies support a greater risk for substance use following bariatric surgery, including an increased use of opioid medications. The present study is the first to study morphine self-administration in a rat model of RYGB. High fat diet-induced obese (HFD-DIO) rats underwent RYGB (n=14) or sham-surgery with ad libitum HFD (SHAM, n=14) or a restricted amount that resulted in weight matched to the RYGB cohort (SHAM-WM, n=8). An additional normal-diet (ND, n=7), intact (no surgery) group of rats was included. Two months after the surgeries, rats were fitted with jugular catheters and trained on a fixed ratio-2 lick task to obtain morphine intravenously. Both morphine-seeking (number of licks on an empty spout to obtain morphine infusion) and consumption (number of infusion) were significantly greater in RYGB than any control group beginning on day 3 and reached a two-fold increase over a period of two weeks. These findings demonstrate that RYGB increases motivation for taking morphine and that this effect is independent of weight loss. Further research is warranted to reveal the underlying mechanisms and to determine whether increased morphine use represents a risk for opioid addiction following RYGB. Identifying risk factors preoperatively could help with personalized postoperative care to prevent opioid abuse and addiction. PMID:26304761

  19. The Relationship Between Left Ventricular Fractional Shortening and Intravenous Administration of Stem Cells in Laboratory Rabbits Presenting Chronic Myocardial Infarction

    PubMed Central

    POP, IONEL CIPRIAN; GRAD, OVIDIU; PALL, EMOKE; PESTEAN, COSMIN; MIRCEAN, MIRCEA; MIRONIUC, ION AUREL

    2015-01-01

    Background and aims The present study conducted from March 2012 to July 2013 aimed to evaluate from echocardiographic point of view the effects of peripheral intravenous administration of mesenchymal stem cells (MSCs) in laboratory rabbits presenting 30 days old chronic myocardial infarction. Material and methods 30 days after the induction of an acute myocardial infarction in 40 laboratory rabbits by direct ligation of the left anterior descending coronary artery at about 10 mm from the apex, we injected 1×106 MSCs in the auricular vein in a group of 30 rabbits, and a group of 10 rabbits were used as controls. 30 days after the injection of stem cells the left ventricular (LV) fractional shortening (FS) was evaluated by echocardiography and compared with the control rabbits. Results In control rabbits, echocardiography revealed akinesis of apex, interventricular septum kinetics was also impaired, FS being approximately 6%. In 80% (24 rabbits) of the injected rabbits the FS of the LV was significantly greater than in the witness group (26+/−2%, p<0.0001). At 13.3% (4 rabbits) of the injected rabbits the FS of the LV showed no improvement in comparison with the control group (6.5+/−1%). Conclusion An improvement of LV SF 30 days after MSCs were injected(p<0.0001) was noted. We have to further determine if this improvement of the LV function is correlated with any histopathological changes and if it is not lost in time. Also, further studies needs to evaluate if there is any significant change in the overall mortality. PMID:26528044

  20. Aβ anti-idiotypic antibodies are present in intravenous immunoglobulin and are produced in mice following its administration.

    PubMed

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P

    2015-06-01

    The effects of intravenous immunoglobulin (IVIG) products were recently examined in patients with Alzheimer's disease (AD). Although encouraging results were obtained in pilot studies, later trials produced negative results. The rationale for these studies was that IVIG contains antibodies to amyloid-beta (Aβ). However, if Aβ anti-idiotypic antibodies (antibodies which bind to anti-Aβ antibodies) are present in IVIG or induced by its administration, these antibodies could potentially reduce its neuroprotective effects in AD. The objective of this study was to determine if IVIG contained such antibodies. Enzyme-linked immunosorbent assays (ELISAs) measured specific binding of IVIG Gamunex to purified human anti-Aβ IgG. The mean concentration of its Aβ anti-idiotypic antibodies in four experiments was 1.85 μg/mL (18.5 μg/g IgG; range = 1.82-1.89 μg/mL [18.2-18.9 μg/g IgG]), and their mean percentage of specific binding was 72.2% (range = 68.3-75.3%). We then performed ELISAs to determine if antibodies to purified human anti-Aβ were produced in C57BL/6 mice injected with the IVIG product Gammagard in an earlier study. After subtracting the expected immune response to normal human immunoglobulins, the median concentrations of these antibodies were 15.6 ng/mL (range = 1.2-108.2 ng/mL) in pre-treatment sera and 2419.4 ng/mL (range = 327.4-8478.4 ng/mL) in post-treatment sera. These results indicate that specific Aβ anti-idiotypic antibodies are detectable in IVIG and may be induced in mice by its administration. The presence of Aβ anti-idiotypic antibodies in IVIG products might decrease neuroprotective effects of their anti-Aβ antibodies in AD. PMID:25392130

  1. [Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

    PubMed

    Tsushima, K; Sakata, Y; Shiratori, Y; Sakamoto, J; Koeda, J; Yamada, Y; Soma, N; Tamura, K; Yoshiwara, A; Soma, Y

    1991-12-01

    We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed. PMID:1660702

  2. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eight cattle (288 +/- 22 kg) were treated with 2.2 mg/kg of flunixin in a cross-over design using subcutaneous (SC) and intravenous (IV) administration. The limit of detection (LOD) was 0.42 ng/mL and the working range was 0.76 - 66.4 ng/mL for ELISA when adjusted for dilution. The linear calibrat...

  3. Gr-1+CD11b+ myeloid cells efficiently home to site of injury after intravenous administration and enhance diabetic wound healing by neoangiogenesis

    PubMed Central

    Tong, Xiaozhe; Lv, Gang; Huang, Jianhua; Min, Yongfen; Yang, Li; Lin, Pengnian Charles

    2014-01-01

    Vascularization is an important factor that affects diabetic wound healing. There is increasing evidence that myeloid cell lineages play a role in neovascularization. In this study, the efficiency of Gr-1+CD11b+ myeloid cells to home to the site of injury and enhance diabetic wound healing by neoangiogenesis after intravenous administration was investigated. Gr-1+CD11b+ myeloid cells were injected into tail vein after establishment of dorsal window chamber, hindlimb ischaemia and ear-punch injury in diabetic or non-diabetic mice. The Gr-1+CD11b+ myeloid cells efficiently homed to the site of injury after intravenous administration and increased neoangiogenesis. The chemokine receptor type 4 (CXCR4) is robustly expressed by Gr-1+CD11b+ myeloid cells. Inhibition of CXCR4 decreases the homing ability of Gr-1+CD11b+ myeloid cells to the site of injury, which indicates that the CXCR4/SDF-1 axis plays an important role in the homing of Gr-1+CD11b+ myeloid cells to the site of injury. In addition, Gr-1+CD11b+ myeloid cells were found to improve blood flow recovery of ischaemic limb and enhance wound healing in diabetic mice by neoangiogenesis after intravenous administration. Taken together, the results of this study suggest that Gr-1+CD11b+ myeloid cells may serve as a potential cell therapy for diabetic wound healing. PMID:24645717

  4. Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis

    PubMed Central

    Manwani, Deepa; Chen, Grace; Carullo, Veronica; Serban, Stelian; Olowokure, Olugbenga; Jang, Jungeun; Huggins, Matthew; Cohen, Hillel W.; Billett, Henny; Atweh, George F.; Frenette, Paul S.; Shi, Patricia A.

    2015-01-01

    Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200–400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600–800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function. PMID:25616042

  5. LH release and ovulatory response after intramuscular, intravenous, and intrauterine administration of β-nerve growth factor of seminal plasma origin in female llamas.

    PubMed

    Silva, M; Fernández, A; Ulloa-Leal, C; Adams, G P; Berland, M A; Ratto, M H

    2015-10-15

    The objective of the study was to compare the pituitary and ovarian responses after intramuscular, intravenous, or intrauterine administration of β-nerve growth factor (β-NGF) of seminal plasma origin (SP-NGF) in llamas. In experiment 1, mature female llamas with a growing follicle of 7 mm or greater were assigned randomly to four groups (n = 7/group) and given 2 mg of purified SP-NGF in a volume of 2 mL by (1) intramuscular administration, (2) intravenous administration, and (3) intrauterine infusion, or (4) intrauterine infusion of 2 mL of PBS (negative control). Because ovulations were not detected after intrauterine infusion in experiment 1, a second experiment was done to determine if a higher dose of SP-NGF given by intrauterine infusion, similar to a natural dose during copulation, will elicit an ovulatory response. In experiment 2, llamas with a growing follicle of 7 mm or greater were assigned randomly to three groups (n = 6/per group) given an intrauterine infusion of (1) 4 mL of raw seminal plasma, (2) 4 mL of PBS containing 20 mg of purified llama SP-NGF, or 3) 4 mL of PBS (negative control). In both experiments, the ovaries were examined daily by transrectal ultrasonography using a B-mode scanner and power Doppler mode to detect ovulation and to monitor CL growth, regression, and vascularization. Blood samples were collected to determine plasma LH and progesterone concentrations. In experiment 1, only llamas treated by intramuscular or intravenous administration of SP-NGF ovulated (7 of 7 and 6 of 7, respectively). Plasma LH concentration did not differ between the intramuscular and intravenous SP-NGF-treated groups, nor did CL diameter, CL vascularization, or plasma progesterone concentration profiles. In experiment 2, the ovulation rate was 100% for llamas treated by intrauterine infusion of raw seminal plasma or llama SP-NFG, whereas no ovulations were detected in females treated with PBS. Plasma LH concentrations did not differ between groups

  6. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration

    PubMed Central

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with ‘protective’ serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics. PMID:23257273

  7. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration.

    PubMed

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with 'protective' serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics. PMID:23257273

  8. Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

    PubMed Central

    Moslemi, Mohammad K; Movahed, Seyed M Moosavi; Heidari, Akram; Saghafi, Hossein; Abedinzadeh, Mehdi

    2010-01-01

    Background Unrestricted antibiotic use is very common in Iran. As a result, emergence of resistant organisms is commonplace. Antibiotic prophylaxis in surgery consists of a short antibiotic course given immediately before the procedure in order to prevent development of a surgical site infection. The basic principle of prophylaxis is to maintain effective concentrations of an antibiotic active against the commonest pathogens during the entire surgery. Materials and methods We prospectively investigated 427 urologic surgery cases in our department between August 2008 and September 2009 (Group1). As reference cases, we retrospectively reviewed 966 patients who underwent urologic surgery between May 2004 and May 2008 (Group 2) who were administered antibiotics without any restriction. Prophylactic antibiotics such as cefazolin were administered intravenously according to our protocol. Postoperative body temperature, peripheral white blood cell counts, urinalysis, and urine culture were checked. Results To judge perioperative infections, wound condition and general condition were evaluated in terms of surgical site infection, as well as remote infection and urinary tract infection, up to postoperative day 30. Surgical site infection was defined as the presence of swelling, tenderness, redness, or drainage of pus from the wound, superficially or deeply. Remote infection was defined as occurrence of pneumonia, sepsis, or urinary tract infection. Perioperative infection rates (for surgical site and remote infection) in Group 1 and Group 2 were nine of 427 (2.6%) and 24 of 966 (2.5%), respectively. Surgical site infection rates of categories A and B in Group 1 were 0 and two (0.86%), respectively, while those in Group 2 were 0 and five (0.92%), respectively. There was no significant difference in infection rates in terms of remote infection and surgical site infection between Group 1 and Group 2 (P = 0.670). The amounts, as well as the prices, for intravenously

  9. Urinary Concentrations and Antibacterial Activity of BAL30072, a Novel Siderophore Monosulfactam, against Uropathogens after Intravenous Administration in Healthy Subjects.

    PubMed

    Straubinger, Marion; Blenk, Holger; Naber, Kurt G; Wagenlehner, Florian M E

    2016-06-01

    This annex study to a phase 1 study aimed to correlate urinary concentrations and bactericidal titers (UBTs) of BAL30072, a novel siderophore monosulfactam, in healthy subjects in order to evaluate which dosage of BAL30072 should be investigated in a clinical study on complicated urinary tract infection (UTI). Three cohorts of a total of 19 healthy male subjects were included in the add-on study and received the following BAL30072 dosages. The 1st cohort received 1 g once a day (q.d.) intravenously (i.v.) (1 h) on day 1 and 1 g thrice daily (t.i.d.) on day 2, the 2nd cohort received 2 g q.d. i.v. (1 h) on day 1 and 2 g t.i.d. on day 2, and the 3rd cohort received 1 g q.d. i.v. (4-h infusion) on day 8. Urine was collected up to 24 h after drug administration. UBTs were determined for seven Escherichia coli isolates (three wild type [WT], CTX-M-15, TEM-3, TEM-5, NDM-1), two Klebsiella pneumoniae isolates (WT, KPC), one Proteus mirabilis isolate (WT), and two Pseudomonas aeruginosa isolates (WT, VIM-1 plus AmpC). Urine drug concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median urinary excretions of BAL30072 ranged between 38% and 46% (3 cohorts). The median UBTs after i.v. administration of 1 or 2 g q.d. and after 1 or 2 g t.i.d. showed positive UBTs for 24 h after the lowest dosage (1 g q.d.) for 5 of 7 of the Enterobacteriaceae strains and after the higher dosage of 2 g administered i.v. t.i.d. for all strains tested. After i.v. infusion of 1 g over 4 h, positive UBTs were demonstrated for three E. coli strains for up to 12 h, for the K. pneumoniae (KPC) strain for up to 8 h, and for the P. aeruginosa (VIM-1 plus AmpC) strain for up to only 4 h. The minimal bactericidal concentrations (MBCs) of the E. coli (NDM-1) strain and the K. pneumoniae (WT) strain correlated well between broth and urine but did not correlate well for the two P. aeruginosa strains. BAL30072 exhibits positive UBTs for 24 h even after a dosage of 1

  10. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir.

    PubMed

    Zhou, Huicong; He, Zhiliang; Wang, Changdong; Xie, Tingting; Liu, Lin; Liu, Chuanyang; Song, Fangzhou; Ma, Yongping

    2016-01-01

    The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF) and HSV TK/GCV (BF-rTK/GCV). However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV) was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF) expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy. PMID:27275821

  11. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir

    PubMed Central

    Zhou, Huicong; He, Zhiliang; Wang, Changdong; Xie, Tingting; Liu, Lin; Liu, Chuanyang; Song, Fangzhou; Ma, Yongping

    2016-01-01

    The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF) and HSV TK/GCV (BF-rTK/GCV). However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV) was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF) expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy. PMID:27275821

  12. Intravenous leiomyomatosis revisited: an experience of 14 cases at a single medical center.

    PubMed

    Carr, Ryan J; Hui, Pei; Buza, Natalia

    2015-03-01

    Intravenous leiomyomatosis (IVL) is a rare neoplasm of smooth muscle origin with the capacity for distant vascular and/or organ extension. The primary lesion is typically found in the uterus, with the most common extrauterine sites being pelvic/broad ligament vessels, and less often inferior vena cava, right heart chambers, and pulmonary vasculature. Extrauterine involvement can result in direct mass effect or vascular obstruction with associated clinical sequelae. Fourteen cases of IVL were identified in our pathology archives over a 25-yr period. Patient medical records and gross pathologic findings were reviewed. Histologic and related immunohistochemical slides (smooth muscle actin, desmin, CD31, CD34, and CD10) were re-evaluated by 2 gynecologic pathologists to confirm the diagnosis using conventional diagnostic criteria. Patient age at initial diagnosis ranged from 35 to 64 yr (mean: 46.1 yr), with a median age of 45 yr. Four cases demonstrated extrauterine extension, 2 cases were associated with disease recurrence, and 1 case was found to be extrauterine in origin (i.e. arising from the broad ligament). In summary, our study represents the fourth largest IVL cohort in literature to date, and contains the first case of IVL arising from the broad ligament in the absence of a uterine mass. IVL is a rare and potentially underdiagnosed neoplastic condition of smooth muscle origin that may result in significant morbidity when extrauterine vasculature or organs are involved. A high index of suspicion must be maintained, as the histologic diagnosis may be particularly challenging in cases in which the intracaval/intracardiac portion of the tumor is removed before the uterine IVL diagnosis, or a significant interval of time has elapsed since the initial IVL diagnosis was made. Prompt diagnosis combined with surgical excision has been shown to portend an increased survival rate and good overall prognosis in such cases. PMID:25675187

  13. Long-term cyclic intravenous iloprost in systemic sclerosis: clinical experience from a single center.

    PubMed

    Casigliani Rabl, S; Della Rossa, A; Pepe, P; D'Ascanio, A; Mosca, M; Di Vita, A; Bombardieri, S

    2012-01-01

    The aim of the present study was to retrospectively evaluate response to therapy in 73 patients affected by systemic sclerosis (SSc) who underwent long-term cyclic treatment with intravenous iloprost for peripheral vascular involvement (average duration of treatment 54.12±41.04 months). Seventy-three SSc patients were enrolled. Data were collected by reviewing clinical records and by phone or direct interview. Patients underwent a thorough physical examination at the end of follow up. The incidence of severe vascular manifestations was also assessed. Statistical analysis was performed by Wilcoxon's signed rank test and descriptive statistics using Statview software. In this study cohort, 55 of 73 (75.2%) patients had a history of ischemic digital ulcers (DUs); 28 patients (38.4%) had active DUs at the beginning of treatment. Skin ulcers healed completely in 25 of 28 patients (89.3%) at the end of the first treatment. However, 40 of 55 patients (72.6%) relapsed after an average of 24 months. There was a significant correlation between relapse rate and/or number of ulcers and clinical factors (diffuse subset, changes in results of Allen's test, NT-pro BNP levels). The annual incidence of pulmonary arterial hypertension (PAH) was 2.34 (95%CI: 0.94-4.83) per 100 person years, the rate of gangrene was 2.7%, and no cases of scleroderma renal crisis were recorded. The incidence of PAH and of digital gangrene was higher than that observed in unselected SSc case series. These data suggest that our patients treated with iloprost have a higher vascular involvement than large case series of unselected SSc patients. A number of clinical factors are correlated to the severity of vascular involvement and could have an impact on the response to therapy. The clinical significance of these findings requires clarification and further investigation is needed. PMID:22842299

  14. The effects of a single intravenous injection of novel activin A/BMP-2 (AB204) on toxicity and the respiratory and central nervous systems.

    PubMed

    Yoon, Byung-Hak; Lee, Jae Hyup; Na, Kyuheum; Ahn, Chihoon; Cho, Jongho; Ahn, Hyun Chan; Choi, Jungyoun; Oh, Hyosun; Kim, Byong Moon; Choe, Senyon

    2016-07-01

    The purpose of this study was to determine the effects of a single intravenous injection of a novel osteoinductive material, activin A/BMP-2 (AB204), to rodents on toxicity and their respiratory functions and central nervous system (CNS). A single intravenous injection of AB204 was given to Sprague-Dawley (SD) rats in doses of 0, 0.625, 2.5 and 10 mg/kg to observe the mortality rate, the general symptoms for 14 days. The experimental groups were also given 0.2, 0.4 and 0.8 mg/kg of AB204, respectively, and the respiration rate, the tidal volume and the minute volume were measured for 240 min. The experimental groups of imprinting control region (ICR) mice were given a single intravenous injection of 0.2, 0.4 and 0.8 mg/kg of AB204, respectively. Their body temperature was taken and general behaviors were observed to evaluate the effect of AB204 on the CNS for 240 min. The study on toxicity of a single intravenous injection found no death or abnormal symptoms, abnormal findings from autopsy, or abnormal body weight gain or loss in all the experimental groups. No abnormal variation associated with the test substance was observed in the respiration rate, the tidal volume, the minute volume, body temperature or the general behaviors. On the basis of these results, the approximate lethal dose of AB204 for a single intravenous injection exceeds 10 mg/kg for SD rats and a single intravenous injection of ≤0.8 mg/kg AB204 has no effect on their respiratory system for SD rat and no effect on their CNS for ICR mice. PMID:26446865

  15. Chemotherapy by Intravenous Administration of Conjugates of Daunomycin with Monoclonal and Conventional Anti-Rat α -fetoprotein Antibodies

    NASA Astrophysics Data System (ADS)

    Tsukada, Yutaka; Hurwitz, Esther; Kashi, Rina; Sela, Michael; Hibi, Nozomu; Hara, Akihiko; Hirai, Hidematsu

    1982-12-01

    Monoclonal antibodies to rat α -fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.

  16. [The effect of a new drug form for the intravenous administration of vitamin K1 on the blood coagulation system].

    PubMed

    Belozerskaia, G G; Makarov, V A; Petrukhina, G N; Samoĭlov, A V; Kamaev, N O; Seĭfulla, R D

    1992-01-01

    In rabbits with experimental hypocoagulation induced by phenylin, the use of a new dosage form of vitamin K1 for intravenous injections in does of 1 and 5 mg/kg led, in contrast to vicasol in a dose of 0.4 mg/kg, to an increase of the prothrombin index after 2 hours and to its complete normalization after 4 hours. Intravenous injection of vitamin K1 into intact animals did not entail any changes in the activated partial thromboplastin time, thrombin and prothrombin time, in the content of fibrinogen and products of its biotransformation, antithrombin III activity, and fibrinolytic activity or in the count of platelets and their aggregation capacity. PMID:1422449

  17. Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration.

    PubMed

    Lalatsa, A; Schätzlein, A G; Garrett, N L; Moger, J; Briggs, Michael; Godfrey, Lisa; Iannitelli, Antonio; Freeman, Jay; Uchegbu, I F

    2015-01-10

    The clinical development of neuropeptides has been limited by a combination of the short plasma half-life of these drugs and their ultimate failure to permeate the blood brain barrier. Peptide nanofibres have been used to deliver peptides across the blood brain barrier and in this work we demonstrate that the polymer coating of peptide nanofibres further enhances peptide delivery to the brain via the intravenous route. Leucine(5)-enkephalin (LENK) nanofibres formed from the LENK ester prodrug - tyrosinyl(1)palmitate-leucine(5)-enkephalin (TPLENK) were coated with the polymer - N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) and injected intravenously. Peptide brain delivery was enhanced because the GCPQ coating on the peptide prodrug nanofibres, specifically enables the peptide prodrug to escape liver uptake, avoid enzymatic degradation to non-active sequences and thus enjoy a longer plasma half life. Plasma half-life is increased 520%, liver AUC0-4 decreased by 54% and brain AUC0-4 increased by 47% as a result of the GCPQ coating. The increased brain levels of the GCPQ coated peptide prodrug nanofibres result in the pharmacological activity of the parent drug (LENK) being significantly increased. LENK itself is inactive on intravenous injection. PMID:25449808

  18. Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co-glycolide) microcapsules following intravenous administration of high amounts in rats

    PubMed Central

    Ferenz, Katja B.; Waack, Indra N.; Laudien, Julia; Mayer, Christian; Broecker-Preuss, Martina; Groot, Herbert de; Kirsch, Michael

    2014-01-01

    The host response against foreign materials designates the biocompatibility of intravenously administered microcapsules and thus, widely affects their potential for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters, as well as markers of inflammation and indicators of organ damage were carefully evaluated after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))-shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement factors) and developed a mild metabolic acidosis. The observed hypotension emerging immediately after start of capsule infusion was transient and mean arterial blood pressure restored to baseline within 70 min. Microcapsules accumulated in spleen and liver (but not in other organs) and partly occluded hepatic microcirculation reducing sinusoidal perfusion rate by about 20%. Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was tolerated temporarily but associated with severe side effects such as hypotension and organ damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as emulsifier for the preparation of drug carriers designed for intravenous use. PMID:25756002

  19. Comparison between the in vivo rate of metabolism of prostaglandin I2 and its blood-pressure-lowering response after intravenous administration in the rat.

    PubMed

    Pace-Asciak, C R; Rosenthal, A; Domazet, Z

    1979-07-27

    Intravenous bolus injection of prostaglandin I2 in the Inactin-anaesthetised rat produces a slow dose-dependant vasodepression which reaches maximum approximately 15 s. after injection. Administration of 9 beta-[3H1]-prostaglandin I2 by the same route followed by serial arterial sampling and TLC analysis revealed a slow conversion into one less polar metabolite starting after 20 s and reaching 40% by two minutes in the circulation. These experiments indicate that prostaglandin I2 survives pulmonary transit for a sufficiently long time to elicit a biological action. Thus its continuous systemic vascular synthesis could play an important role in the control of hypertension. PMID:383157

  20. Pharmacokinetic profile of cefbuperazone in healthy Chinese volunteers after single and multiple drip intravenous infusion by HPLC-MS/MS.

    PubMed

    Liu, Dongbo; Geng, Taohua; Wang, Yiya; Ding, Li

    2016-09-10

    A selective and reproducible HPLC-MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1×50mm, 3.5μm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250μg/mL in plasma and 20.0-5000μg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7±8.1μg/mL, 86.7±12.7μg/mL and 168±14μg/mL in 0.5, 1.0 and 2.0g dose groups respectively, at 60min after the start of infusion. The half-life (t1/2) was between 1.8-1.9h, and the elimination constant (kel) was between 0.36-0.39h(-1). The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5-2.0g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5g to 2.0g. PMID:27394175

  1. Pharmacokinetics and Safety of a Single Intravenous Dose of myo-Inositol in Preterm Infants of 23 to 29 weeks

    PubMed Central

    Phelps, Dale L.; Ward, Robert M.; Williams, Rick L.; Watterberg, Kristi L.; Laptook, Abbot R.; Wrage, Lisa A.; Nolen, Tracy L.; Fennell, Timothy R.; Ehrenkranz, Richard A.; Poindexter, Brenda B.; Cotten, C. Michael; Hallman, Mikko K.; Frantz, Ivan D.; Faix, Roger G.; Zaterka-Baxter, Kristin M.; Das, Abhik; Ball, M. Bethany; O’Shea, T. Michael; Lacy, Conra Backstrom; Walsh, Michele C.; Shankaran, Seetha; Sánchez, Pablo J.; Bell, Edward F.; Higgins, Rosemary D.

    2014-01-01

    Background Myo-inositol given to preterm infants with respiratory distress has reduced death, increased survival without bronchopulmonary dysplasia (BPD) and reduced severe retinopathy of prematurity (ROP) in 2 randomized trials. Pharmacokinetic (PK) studies in extremely preterm infants are needed prior to efficacy trials. Methods Infants of 23–29 weeks gestation were randomized to a single intravenous (IV) dose of inositol at 60 or 120 mg/kg or placebo. Over 96 h, serum levels (sparse sampling population PK) and urine inositol excretion were determined. Population PK models were fit using a nonlinear mixed effects approach. Safety outcomes were recorded. Results A 1-compartment model that included factors for endogenous inositol production, allometric size based on weight, gestational age (GA) strata and creatinine clearance fit the data best. The central volume of distribution was 0.5115 l/kg, the clearance 0.0679 l/kg/h, endogenous production 2.67 mg/kg/h and the half life 5.22 h when modeled without the covariates. During the first 12 h renal inositol excretion quadrupled in the 120 mg/kg group, returning to near baseline after 48 h. There was no diuretic side-effect. No significant differences in adverse events occurred between the 3 groups (p > 0.05). Conclusions A single compartment model accounting for endogenous production satisfactorily described the PK of IV inositol. PMID:24067395

  2. Efficacy and Tolerability of a GD2-Directed Trifunctional Bispecific Antibody in a Preclinical Model: Subcutaneous Administration Is Superior to Intravenous Delivery.

    PubMed

    Deppisch, Nina; Ruf, Peter; Eissler, Nina; Neff, Frauke; Buhmann, Raymund; Lindhofer, Horst; Mocikat, Ralph

    2015-08-01

    Trifunctional bispecific antibodies (trAb) are novel anticancer drugs that recruit and activate different types of immune effector cells at the targeted tumor. Thus, tumor cells are effectively eliminated and a long-lasting tumor-specific T-cell memory is induced. The trAb Ektomab is directed against human CD3 on T cells and the tumor-associated ganglioside GD2, which is an attractive target for immunotherapy of melanoma in humans. To optimize clinical applicability, we studied different application routes with respect to therapeutic efficacy and tolerability by using the surrogate trAb Surek (anti-GD2 × anti-murine CD3) and a murine melanoma engineered to express GD2. We show that subcutaneous injection of the trAb is superior to the intravenous delivery pathway, which is the standard application route for therapeutic antibodies. Despite lower plasma levels after subcutaneous administration, the same tumor-protective potential was observed in vivo compared with intravenous administration of Surek. However, subcutaneously delivered Surek showed better tolerability. This could be explained by a continuous release of the antibody leading to constant plasma levels and a delayed induction of proinflammatory cytokines. Importantly, the induction of counter-regulatory mechanisms was reduced after subcutaneous application. These findings are relevant for the clinical application of trifunctional bispecific antibodies and, possibly, also other immunoglobulin constructs. Mol Cancer Ther; 14(8); 1877-83. ©2015 AACR. PMID:26063765

  3. Pulsatile intravenous gonadotropin-releasing hormone administration averts fasting-induced hypogonadotropism and hypoandrogenemia in healthy, normal weight men.

    PubMed

    Aloi, J A; Bergendahl, M; Iranmanesh, A; Veldhuis, J D

    1997-05-01

    Fasting or severe caloric restriction in the human or experimental animal suppresses serum LH and sex steroid concentrations. In healthy men undergoing prolonged (5-day) nutrient deprivation, the daily LH secretion rate, the mass of LH secreted per burst, and the serum testosterone concentration fall markedly, with no decrease in responsiveness to a single bolus of GnRH. Here we test the hypothesis that the hypogonadotropic hypoandrogenemia accompanying fasting reflects decreased endogenous GnRH release. To this end, six healthy young men were studied on a fed day and during two 83-h fasting sessions with concurrent saline or pulsatile GnRH administration (100 ng/kg, i.v., every 90 min for 24 h) followed by a single bolus of 10 microg GnRH, i.v., to evaluate pituitary responsiveness. We employed a highly sensitive LH immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay, and deconvolution analysis to calculate in vivo LH secretory burst frequency, amplitude, duration, mass, and LH half-life. Fasting resulted in 30-50% declines in serum total and free testosterone and LH concentrations, and a 3-fold decrease in the calculated 24-h LH secretion rate (fed, 42 +/- 12; fasting, 14 +/- 1.9 U/L distribution volume x day; mean +/- SEM; P < 0.05, by ANOVA). Reduced LH secretion was accounted for by dual mechanisms, viz. a fall in both the apparent number of computer-resolved LH secretory bursts per 24 h (fed, 16 +/- 1.1; fasting, 10 +/- 1.2; P < 0.01) and the mass of LH secreted per burst (fed, 2.5 +/- 0.5; fasting, 1.5 +/- 0.1 U/L; P < 0.05). Fasting also decreased the mean value of the 24-h (nyctohemeral) rhythm in serum LH concentrations and reduced the approximate entropy (disorderliness) of LH release. Exogenous pulsatile GnRH injections prevented both the reduction in the calculated daily LH secretion rate (fed, 42 +/- 12; fasting plus GnRH, 64 +/- 16 IU/L; P = NS) and the decline in serum testosterone concentrations (fed, 556 +/- 71 ng

  4. Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration

    PubMed Central

    Miyazawa, Taiki; Nakagawa, Kiyotaka; Harigae, Takahiro; Onuma, Ryo; Kimura, Fumiko; Fujii, Tomoyuki; Miyazawa, Teruo

    2015-01-01

    Purpose Biodegradable nanoparticles (NPs) composed of poly(D, L-lactide-co-glycolide) (PLGA) have attracted considerable attention as delivery systems of drugs and antioxidative compounds, such as β-carotene (BC). Intravenous (IV) administration of BC-containing PLGA-NPs (BC-PLGA-NPs) coated with polysorbate 80 (PS80) has been shown to effectively deliver BC to the brain. However, the whole-body distribution profile of BC is still not clear. Therefore, we investigated the accumulation of BC in various organs, including the brain, following IV administration of PS80-coated BC-PLGA-NPs in rats. Methods PS80-coated and uncoated BC-PLGA-NPs were prepared by solvent evaporation, and administered intravenously to Sprague Dawley rats at a BC dose of 8.5 mg/rat. Accumulation of BC in various organs (brain, heart, liver, lungs, and spleen) and blood plasma was evaluated by high performance liquid chromatography with ultraviolet (UV) detection, 1 hour after administration. Results We prepared PS80-coated BC-PLGA-NPs with an entrapment efficiency of 14%, a particle size of 260 nm, and a zeta potential of −26 mV. Coating with PS80 was found to result in significant accumulation of BC in the lungs, rather than in the brain and other tissues. Further, plasma levels of BC in the PS80-coated BC-PLGA-NP group were much lower than those of the uncoated BC-PLGA-NP group. Conclusion Following IV administration, PS80-coated BC-PLGA-NPs are quickly transferred from plasma circulation to the lungs, rather than the brain. Significant accumulation of BC in the lungs may be useful for health-related applications. PMID:26664113

  5. Pharmacokinetics of a single intravenous enrofloxacin dose in scimitar-horned oryx (Oryx dammah).

    PubMed

    Gamble, K C; Boothe, D M; Jensen, J M; Heatley, J J; Helmick, K E

    1997-03-01

    Based on a 1.3 mg/kg mean dosage determined by metabolic energy scaling, enrofloxacin pharmacokinetics of a single i.v. dose of enrofloxacin in five adult scimitar-horned oryx (Oryx dammah) were determined. Drug concentration versus time curves were best fit by residual analysis to a one-compartment open model with a maximum (mean +/- SD) serum concentration after distribution of 1.887 +/- 0.632 micrograms/ml and an elimination half-life of 41.2 +/- 27.5 min. Model-independent parameters were area under the curve (173.63 +/- 147.5 micrograms.min/ml), mean volume of distribution (steady state) (0.80 +/- 0.30 L/kg), clearance (12.07 +/- 7.12 ml/min/kg), and residence time (77.22 +/- 72.8 min). Mean serum enrofloxacin concentrations reached the recommended minimum inhibitory concentration (1.0 micrograms/ml). Drug concentrations remained above the minimum inhibitory concentration of most sensitive bacteria (0.5 micrograms/ml) consistently for 90 min. Based on this study, enrofloxacin would have to be administered parenterally to scimitar-horned oryx at 1.6 mg/kg every 6-8 hr (minimally) to maintain appropriate serum concentrations against susceptible bacteria. The metabolic energy scaled dosed regiment from this study appeared to be too low for the oryx. PMID:9226614

  6. Disposition, metabolism, and excretion of [14C]doripenem after a single 500-milligram intravenous infusion in healthy men.

    PubMed

    Cirillo, Iolanda; Mannens, Geert; Janssen, Cor; Vermeir, Marc; Cuyckens, Filip; Desai-Krieger, Daksha; Vaccaro, Nicole; Kao, L Mark; Devineni, Damayanthi; Redman, Rebecca; Turner, Kenneth

    2008-10-01

    In this open-label, single-center study, eight healthy men each received a single 500-mg dose of [(14)C]doripenem, containing 50 microCi of [(14)C]doripenem, administered as a 1-h intravenous infusion. The concentrations of unchanged doripenem and its primary metabolite (doripenem-M-1) resulting from beta-lactam ring opening were measured in plasma and urine by a validated liquid chromatography method coupled to a tandem mass spectrometry assay. Total radioactivity was measured in blood, plasma, urine, and feces by liquid scintillation counting. Further metabolite profiling was conducted on urine samples using liquid chromatography coupled to radiochemical detection and high-resolution mass spectrometry. Unchanged doripenem and doripenem-M-1 accounted for means of 80.7% and 12.7% of the area under the plasma total-radioactivity-versus-time curve (area under the concentration-time curve extrapolated to infinity) and exhibited elimination half-lives of 1.1 and 2.5 h, respectively. Total clearance of doripenem was 16 liters/h, and renal clearance was 12.5 liters/h. At 7 days after the single dose, 95.3% of total doripenem-related radioactivity was recovered in urine and 0.72% in feces. A total mean of 97.2% of the administered dose was excreted in the urine as unchanged doripenem (78.7% +/- 5.7%) and doripenem-M-1 (18.5% +/- 2.6%). Most of the urinary recovery occurred within 4 h of dosing. Three additional minor metabolites were identified in urine: the glycine and taurine conjugates of doripenem-M-1 and oxidized doripenem-M-1. These results show that doripenem is predominantly eliminated in urine as unchanged drug, with only a fraction metabolized to doripenem-M-1 and other minor metabolites. PMID:18644951

  7. [How to control postoperative pain: intravenous route].

    PubMed

    Occella, P; Vivaldi, F

    2003-12-01

    Intravenous administration of analgesic drugs is one of the most common ways to control post-operative pain. It can be used in almost all kinds of surgical interventions and particularly those of medium and high complexity. Besides, when other techniques are contraindicated because of clinical and/or managing problems, intravenous way finds its best application. Among analgesic drugs NSAID (ketorolac) and opioids (tramadol, morphine, buprenorphine) are most frequently used. As to administration techniques, elastomeric pump is, according to personal experience, a simple-to-manage, practical and precise device with lower cost respect to other administration set. Elastomeric pump is a single use reservoir that allows continuous administration of drugs with a uniform pre-set infusion speed. Finally, guide-lines, showing pre-load and infusion doses of analgesic drugs, based on pain intensity, are presented. PMID:14663417

  8. Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves.

    PubMed

    Camargo, F C; Robinson, N E; Dirikolu, L; Berney, C; Eberhart, S; Derksen, F J; Lehner, A F; May, J; Hughes, C; Tobin, T

    2008-12-01

    Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroSpray Ionization, positive mode - Liquid Chromatography - Mass Spectrometry - Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies. PMID:19000271

  9. Pharmacokinetics of a single dose of intravenous and oral meloxicam in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

    PubMed

    Lacasse, Claude; Gamble, Kathryn C; Boothe, Dawn M

    2013-09-01

    Pharmacokinetic data were determined after a single dose of meloxicam in red-tailed hawks (RTH; Buteo jamaicensis) and great horned owls (GHO; Bubo virginianus). In a nonrandomized crossover design, individual birds of each species received 1 dose of intravenous meloxicam (0.5 mg/kg i.v.; n = 7 for each species) followed by a 2-week washout period, and then each received 1 dose of oral meloxicam (0.5 mg/kg PO; n = 5 for each species). Blood samples were collected intermittently after administration, and meloxicam was detected in plasma by high-performance liquid chromatography. Time versus plasma concentration data were subjected to noncompartmental analysis. Red-tailed hawks were determined to have the shortest elimination half-life for meloxicam (0.49 +/- 0.5 hours) of any species documented. Great horned owls also eliminated meloxicam very rapidly (0.78 +/- 0.52 hours). Great horned owls achieved higher plasma concentrations (368 +/- 87 ng/mL) of meloxicam than RTH (182 +/- 167 ng/mL) after oral administration, although RTH had a markedly higher volume of distribution (832 +/- 711 mL/kg) than GHO (137.6 +/- 62.7 mL/kg). The differences in meloxicam pharmacokinetics between these 2 raptor species supports the need for species-dependent studies and underlines the challenges of extrapolating drug dosages between species. Results of this study suggest that the current recommended once-daily dosing interval of oral meloxicam is unlikely to maintain plasma concentrations anticipated to be therapeutic in either RTH or GHO, and practical dosing options are questionable for this nonsteriodal anti-inflammatory drug in these raptor species. PMID:24344511

  10. Whole body and brain distribution of [3H]cyclic [D-Pen2,D-Pen5] enkephalin after intraperitoneal, intravenous, oral and subcutaneous administration.

    PubMed

    Weber, S J; Greene, D L; Hruby, V J; Yamamura, H I; Porreca, F; Davis, T P

    1992-12-01

    The route of administration of a given drug can have a significant influence upon whole body distribution. The present study examined whole body distribution of the delta opioid receptor-selective peptide [3H]DPDPE in male CD1 mice after administration by several routes. Additionally, we describe regional brain distribution of [3H]DPDPE after i.v. administration with and without pretreatment with naloxone or the selective delta receptor antagonist naltrindole. Finally, characterization of the inherent enzymatic stability of DPDPE was also examined. Intravenous administration results in a significantly large amount of [3H]DPDPE in the small intestine and flush at 15 and 30 min postadministration, suggesting rapid biliary excretion. The highest level in the brain after i.v. administration occurred at 60 min (0.08%). After i.p. and s.c. administration, large amounts of [3H]DPDPE were found in the small intestine and flush, but not until 60 min postadministration, suggesting a slower rate of absorption from the site of administration. The i.p. and s.c. groups' brain levels peaked at 120 min (0.07 and 0.09%, respectively). The highest levels in the brain after p.o. administration were seen at 240 min (0.03%). Examination of regional brain distribution data showed no significant difference in the levels of [3H]DPDPE between brain regions at any time point studied. However, naloxone pretreatment resulted in significant reductions of [3H]DPDPE in all brain regions at 5 and 10 min. Naltrindole pretreatment resulted in significant reductions in the frontal cortex and striatum at 5 and/or 10 min postadministration, but had no effect on [3H]DPDPE levels in cerebellum, hippocampus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1469637

  11. Application of vasoactive and matrix-modifying drugs can improve polyplex delivery to tumors upon intravenous administration.

    PubMed

    Durymanov, Mikhail O; Yarutkin, Alexey V; Bagrov, Dmitry V; Klinov, Dmitry V; Kedrov, Alexander V; Chemeris, Nikolay K; Rosenkranz, Andrey A; Sobolev, Alexander S

    2016-06-28

    Low efficacy of cationic polymer-based formulations (polyplexes) for systemic gene delivery to tumors remains the crucial concern for their clinical translation. Here we show that modulating the physiological state of a tumor using clinically approved pharmaceuticals can improve delivery of intravenously injected polyplexes to murine melanoma tumors with different characteristics. Direct comparison of drugs with different mechanisms of action has shown that application of nitroglycerin or losartan improved extravasation and tumor uptake of polyplex nanoparticles, whereas angiotensin II had almost no effect on polyplex accumulation and microdistribution in the tumor tissue. Application of nitroglycerin and losartan caused from 2- to 6-fold enhanced efficacy of polyplex-mediated gene delivery depending on the tumor model. The results obtained on polyplex behavior in tumor tissues depending on physiological state of the tumor can be relevant to optimize delivery of polyplexes and other nanomedicines with similar physicochemical properties. PMID:27072027

  12. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers

    PubMed Central

    Barbour, April M; Sarov-Blat, Lea; Cai, Gengqian; Fossler, Michael J; Sprecher, Dennis L; Graggaber, Johann; McGeoch, Adam T; Maison, Jo; Cheriyan, Joseph

    2013-01-01

    Aims The purpose of this study was to establish safety and tolerability of a single intravenous (IV) infusion of a p38 mitogen-activated protein kinase inhibitor, losmapimod, to obtain therapeutic levels rapidly for a potential acute coronary syndrome indication. Pharmacokinetics (PK) following IV dosing were characterized, and pharmacokinetic/pharmacodynamic (PK/PD) relationships between losmapimod and phosphorylated heat shock protein 27 (pHSP27) and high-sensitivity C-reactive protein were explored. Methods Healthy volunteers received 1 mg losmapimod IV over 15 min (n = 4) or 3 mg IV over 15 min followed by a washout period and then 15 mg orally (PO; n = 12). Pharmacokinetic parameters were calculated by noncompartmental methods. The PK/PD relationships were explored using modelling and simulation. Results There were no deaths, nonfatal serious adverse events or adverse events leading to withdrawal. Headache was the only adverse event reported more than once (n = 3 following oral dosing). Following 3 mg IV and 15 mg PO, Cmax was 59.4 and 45.9 μg l−1 and AUC0–∞ was 171.1 and 528.0 μg h l−1, respectively. Absolute oral bioavailability was 0.62 [90% confidence interval (CI) 0.56, 0.68]. Following 3 mg IV and 15 mg PO, maximal reductions in pHSP27 were 44% (95% CI 38%, 50%) and 55% (95% CI 50%, 59%) occurring at 30 min and 4 h, respectively. There was a 17% decrease (95% CI 9%, 24%) in high-sensitivity C-reactive protein 24 h following oral dosing. A direct-link maximal inhibitory effect model related plasma concentrations to pHSP27 concentrations. Conclusions A single IV infusion of losmapimod in healthy volunteers was safe and well tolerated, and may potentially serve as an initial loading dose in acute coronary syndrome as rapid exposure is achieved. PMID:23215699

  13. Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

    PubMed

    Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

    2016-09-01

    Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats. PMID:26730489

  14. Potentiation of the pressor effect of oral and intravenous tyramine during administration of the selective MAO-A inhibitor moclobemide in healthy volunteers.

    PubMed

    Wijnands, S; Chang, P C; Blauw, G J; van den Krogt, J; Gieschke, R; Schoerlin, M P; van Brummelen, P

    1989-01-01

    The interaction between tyramine and the new short-acting and reversible mono amine oxidase inhibitor moclobemide was investigated in a double-blind placebo-controlled study in six healthy volunteers. There were two consecutive study periods of 8 days during which the subjects received moclobemide three x 200 mg daily or placebo. On day 5 of each study period changes in systolic blood pressure (SBP) were determined after incremental intravenous bolus doses of tyramine and on days 6, 7 and 8 changes in SBP were determined after oral tyramine (100, 200 and 300 mg, respectively). Oral tyramine was administered together with a standard breakfast, before which moclobemide had been given. On days 5- 8 blood was taken for determination of blood drug levels. On days 6-8 blood samples were taken before and at 15, 30 and 45 min after tyramine administration for determination of plasma tyramine and plasma norepinephrine concentrations. When SBP had increased by approximately 30 mmHg no further doses of either intravenous or oral tyramine were given. Moclobemide was well tolerated by all subjects. Plasma trough levels of moclobemide were within the therapeutic range. The tyramine induced increases in SBP were greater during moclobemide than during placebo. After intravenous tyramine the dose-response curve for SBP was shifted to the right by a factor of approximately 3. When compared to placebo the pressor response to 100 mg tyramine orally was not significantly different, but the pressor response to the other two doses was enhanced during moclobemide. PMID:22156310

  15. Intravenous paracetamol (acetaminophen).

    PubMed

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text]. PMID:19192939

  16. Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

    PubMed

    Erb, Suzanne; McPhee, Matthew; Brown, Zenya J; Kupferschmidt, David A; Song, Lifang; Lovejoy, David A

    2014-08-01

    The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors. PMID:24768621

  17. Efficacy and Safety of Intracoronary versus Intravenous Administration of Tirofiban during Percutaneous Coronary Intervention for Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Jing, Quanmin; Liu, Yingfeng; Liu, Peng

    2015-01-01

    Background Percutaneous coronary intervention (PCI) is known as the most effective treatment for acute coronary syndrome (ACS). However, without proper therapy and patient management, stent thrombosis after PCI may lead to another myocardial infarction. In addition to aspirin and clopidogrel, tirofiban is often used as an antiplatelet therapy in patients with ACS. To date, there has been no comprehensive evaluation of the efficacy and safety of intracoronary (IC) tirofiban administration for ACS patients undergoing PCI compared with intravenous (IV) administration. Therefore, this meta-analysis was conducted to investigate the clinical efficiency and safety of IC versus intravenous (IV) tirofiban in ACS patients undergoing PCI. Methods We searched PubMed and Medline for randomized controlled trials (RCTs) comparing IC versus IV administration of tirofiban in ACS patients undergoing PCI. We evaluated the effects of tirofiban on thrombolysis in myocardial infarction (TIMI) grade 3 flow after PCI, TIMI myocardial perfusion grade 3 (TMP grade 3), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACE), target vessel revascularization (TVR), death, reinfarction and adverse drug effects (specifically bleeding events). Results Seven trials involving 1,027 patients were included in this meta-analysis. IC administration of tirofiban significantly increased TIMI grade 3 flow (OR 2.11; 95% CI 1.02 to 4.37; P = 0.04) and TMP grade 3 (OR 2.67; 95% CI 1.09 to 6.49; P = 0.03, I2 = 64%) while reducing MACE (OR 0.46, 95% CI: 0.28 to 0.75; P = 0.002) compared with IV administration of tirofiban. No significant differences were observed in the occurrence of TVR, death, reinfarction and the incidence of bleeding events between the two groups. Conclusions This meta-analysis supports the use of IC over IV administration of tirofiban in patients with ACS to improve TIMI flow, TMP flow and MACE. However, there was no statistically significant difference in

  18. The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

    PubMed

    Koksal, Guniz Meyancı; Erbabacan, Emre; Tunali, Yusuf; Karaoren, Gulsah; Vehid, Suphi; Oz, Huseyin

    2014-01-01

    Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition. PMID:24561970

  19. The in vitro effective antiviral action of povidone-iodine (PVP-I) may also have therapeutic potential by its intravenous administration diluted with Ringer's solution.

    PubMed

    Sabracos, Labros; Romanou, Solomi; Dontas, Ismene; Coulocheri, Stavroula; Ploumidou, Kathrin; Perrea, Despina

    2007-01-01

    The use of povidone-iodine (PVP-I) is well known in clinical medical practice. In vitro studies of cell cultures infected by HIV and H5N1 virus have shown that PVP-I has an antiviral action, while the cell hosts were not affected and survived. It is therefore worth investigating whether PVP-I, diluted with Ringer's solution, may have a therapeutic effect by parenteral administration. Specifically, the question is whether small concentrations of intravenous PVP-I could be well tolerated by the human organism, and in addition, if it would be possible to detect a beneficial activity. Its intravenous use may have a potential value against infections (by microbes, viruses, fungi and parasites), as well as an anti-inflammatory activity, especially in cases where antibiotics are ineffective. It could be used as a blood disinfectant, for treating burns, for the prevention of cancer, for the therapy of H5N1 influenza after its mutation, and other potential applications. PMID:17113717

  20. Comparative observations of fever and associated clinical hematological and blood biochemical changes after intravenous administration of staphylococcal enterotoxins B and F (toxic shock syndrome toxin-1) in goats.

    PubMed Central

    Van Miert, A S; Van Duin, C T; Schotman, A J

    1984-01-01

    The present investigation was undertaken to examine the characteristics of purified toxic shock syndrome toxin-1 (staphylococcal enterotoxin F) given intravenously to dwarf goats (dose, 0.02 to 20 micrograms kg-1). Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and hematological values were studied and compared with the changes seen after intravenous administration of staphylococcal enterotoxin B (dose, 0.02 to 0.5 micrograms kg-1). Similar changes such as fever, tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and a decrease in serum alkaline phosphatase activity were observed. In contrast to the effects of toxic shock syndrome toxin-1, staphylococcal enterotoxin B induced colic, watery diarrhea with pseudomembranes, hemoconcentration, and a more pronounced increase in blood urea nitrogen. The results obtained demonstrate that (i) in the goat staphylococcal enterotoxin B is much more potent than toxic shock syndrome toxin-1 and (ii) the goat is a useful model to study the gastro-intestinal effects caused by staphylococcal enterotoxin B. The present finding that no clear relationship could be found between the temperature response and the alterations in zinc and iron levels in plasma support the theory that the febrile reactions and the changes in plasma trace metals are mediated by different polypeptides released by activated macrophages. PMID:6500695

  1. Single dose testosterone administration reduces loss chasing in healthy females.

    PubMed

    Wu, Yin; Liu, Jinting; Qu, Lujing; Eisenegger, Christoph; Clark, Luke; Zhou, Xiaolin

    2016-09-01

    Testosterone has been linked to modulation of impulsivity and risky choice, potentially mediated by changes in reward or punishment sensitivity. This study investigated the effect of testosterone on risk-taking and the adjustment of risk-taking on trials following a gain or a loss. Loss chasing is operationalized herein as the propensity to recover losses by increasing risky choice. Healthy female participants (n=26) received a single-dose of 0.5mg sublingual testosterone in a double-blind, placebo-controlled crossover design. At 240min post-administration, participants performed a gambling task with a high and a low risk option. In the placebo condition, participants were more likely to choose the high risk option following losses compared to wins. This effect was abolished on the testosterone session. Ignoring prior outcomes, no overall changes in risk-taking were observed. Our data indicate that testosterone affects human decision-making via diminishing sensitivity to punishment. PMID:27236486

  2. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    PubMed

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration. PMID:26582164

  3. A recommendation to perform a blood culture before the administration of intravenous antibiotics increased the detection of Staphylococcus aureus bacteremia.

    PubMed

    Jogenfors, A; Stark, L; Svefors, J; Löfgren, S; Malmvall, B-E; Matussek, A

    2014-05-01

    In 2004, the Surviving Sepsis Campaign was launched to increase awareness and improve the outcome of severe sepsis. Accordingly, in Jönköping County, Sweden, a strong recommendation to perform a blood culture before the start of intravenous antibiotic treatment was introduced in 2007. Moreover, a reminder was included in the laboratory report to consult an infectious disease specialist when Staphylococcus aureus was isolated from a blood culture. Retrospectively, patients with at least one blood culture growing S. aureus during 2002 through 2003 (pre intervention n = 58) or during 2008 through 2009 (post intervention n = 100) were included. Medical records were evaluated regarding clinical data and outcome. Blood culture isolates were characterized by antibiotic susceptibility testing (AST) and S. aureus protein A (spa) gene typing. The annual incidence of S. aureus bacteremia (SAB) increased from 28 per 100,000 inhabitants at the pre intervention period to 45 per 100,000 at the post intervention period (p = 0.046). During post intervention, the SAB incidence was significantly higher in men (p = 0.009). The mortality rate during hospital stay was 14 % during pre intervention and 18 % during post intervention (p = 0.47). The most common spa types were t012 and t084. The Surviving Sepsis Campaign resulted in an increased number of detected cases of SAB. The mortality rate was the same before and after the intervention, and no spa type correlated to certain clinical manifestations or mortality. PMID:24249284

  4. A 90-day subchronic toxicity study with sodium formononetin-3'-sulphonate (Sul-F) delivered to dogs via intravenous administration.

    PubMed

    Li, Chunmei; Li, Guisheng; Gao, Yonglin; Sun, Chengfeng; Wang, Xiaoyan

    2016-06-01

    Sodium formononetin-3'-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs. PMID:26924788

  5. Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

    PubMed

    Duplancic, Bozidar; Stambolija, Vasilije; Holjevac, Jadranka; Zemba, Mladen; Balenovic, Igor; Drmic, Domagoj; Suran, Jelena; Radic, Bozo; Filipovic, Marinko; Blagaic, Alenka Boban; Brcic, Luka; Kolenc, Danijela; Grabarevic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

    2014-03-15

    Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone. PMID:24486708

  6. The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs.

    PubMed

    Bell, E T; Devi, J L; Chiu, S; Zahra, P; Whittem, T

    2016-02-01

    Pimobendan is a benzimidazole-pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three-period, nested randomized two-treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography-mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0-∞) and Cmax . Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half-life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described. PMID:25989021

  7. Intravenous administration of bone marrow mononuclear cells alleviates hearing loss after transient cochlear ischemia through paracrine effects.

    PubMed

    Takagi, Taro; Yoshida, Tadashi; Okada, Masahiro; Hata, Ryuji; Hato, Naohito; Gyo, Kiyofumi; Hakuba, Nobuhiro

    2014-05-16

    Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss. PMID:24840930

  8. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin.

    PubMed

    de Castro, Reynaldo Angelo C; de Castro, Jo-Anne A; Barez, Marie Yvette C; Frias, Melchor V; Dixit, Jitendra; Genereux, Maurice

    2007-04-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets < or = 50,000/mm(3)) reveal that the increase in platelet count with anti-D immune globulin (WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option. PMID:17426181

  9. Sub-acute intravenous administration of silver nanoparticles in male mice alters Leydig cell function and testosterone levels

    PubMed Central

    GARCIA, THOMAS X.; COSTA, GUILHERME M. J.; FRANÇA, LUIZ R.; HOFMANN, MARIE-CLAUDE

    2014-01-01

    The aim of this study was to determine whether short-term, in vivo exposure to silver nanoparticles (AgNPs) could be toxic to male reproduction. Low dose (1 mg/kg/dose) AgNPs were intravenously injected into male CD1 mice over 12 days. Treatment resulted in no changes in body and testis weights, sperm concentration and motility, fertility indices, or follicle-stimulating hormone and luteinizing hormone serum concentrations; however, serum and intratesticular testosterone concentrations were significantly increased 15 days after initial treatment. Histologic evaluation revealed significant changes in epithelium morphology, germ cell apoptosis, and Leydig cell size. Additionally, gene expression analysis revealed Cyp11a1 and Hsd3b1 mRNA significantly upregulated in treated animals. These data suggest that AgNPs do not impair spermatogonial stem cells in vivo since treatment did not result in significant decreases in testis weight and sperm concentrations. However, AgNPs appear to affect Leydig cell function, yielding increasing testicular and serum testosterone levels. PMID:24447867

  10. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  11. Intravenous Therapy.

    ERIC Educational Resources Information Center

    Galliart, Barbara

    Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

  12. High-performance liquid chromatographic determination and pharmacokinetic study of apigenin-7-O-β-D-glucoside in rat plasma after intravenous administration.

    PubMed

    Chen, Zaixing; Ying, Xixiang; Meng, Shu; Zhu, Xu; Jiang, Hong; Cao, Qishen; Li, Xuying; Meng, Fanhao

    2011-05-01

    The present study was designed to validate an analytical method based on HPLC for the quantitative measurement of the Apigenin-7-O-β-D-glucoside (AGL) in rat plasma after intravenous administration. HPLC analysis was done using a C18 column, UV detection at 335 nm, and a mobile phase of methanol:0.2% phosphoric acid (1:1, v/v). Good linearity was observed over the range of 0.06-7.20 μg/mL with a lower limit of quantication of 0.06 μg/mL. The intra-and inter-day precision values were below 9.97%. No interference peaks or matrix effects were observed. The method was fully validated and successfully applied to a pharmacokinetic study of AGL. PMID:21656359

  13. Inhibition of trigeminal neurones after intravenous administration of naratriptan through an action at 5-hydroxy-tryptamine (5-HT1B/1D) receptors

    PubMed Central

    Goadsby, Peter J; Knight, Yolande

    1997-01-01

    The observation that 5-hydroxytryptamine (5-HT) is effective in treating acute attacks of migraine when administered intravenously resulted in a research effort that led to the discovery of the 5-HT1B/1D receptor agonist sumatriptan. Clinical experience has shown sumatriptan to be an effective treatment with some limitations, such as relatively poor bioavailability, which naratriptan was developed to address. Increasing bioavailability has been achieved with greater lipophilicity and thus the potential for greater activity in the central nervous system. In this study the increased access to central sites has been exploited in an attempt to characterize the pharmacology of those central receptors with the newer tools available. Trigeminovascular activation was examined in the model of superior sagittal sinus stimulation. Cats were anaesthetized with α-chloralose (60 mg kg−1, intraperitoneal), paralyzed (gallamine 6 mg kg−1, intravenously) and ventilated. The superior sagittal sinus was accessed and isolated for electrical stimulation (250 μs pulses, 0.3 Hz, 100 V) by a mid-line circular craniotomy. The region of the dorsal surface of C2 spinal cord was exposed by a laminectomy and an electrode placed for recording evoked activity from sinus stimulation. Stimulation of the superior sagittal sinus resulted in activation of cells in the dorsal horn of C2. Cells fired with a probability of 0.69±0.1 at a latency of 9.2±0.2 ms. Intravenous (i.v.) administration of naratriptan at clinically relevant doses (30 and 100 μg kg−1), inhibited neuronal activity in trigeminal neurones of the C2 dorsal horn, reducing probability of firing without affecting latency. The effect of naratriptan could be reversed by administration of the selective 5-HT1B/1D receptor antagonist GR127935 (100 μg kg−1, i.v.). These data establish that naratriptan acts on central trigeminal neurones since sagittal sinus stimulation activates axons within the tentorial

  14. Tissue distribution of amino acid- and lipid-brevetoxins after intravenous administration to C57BL/6 mice.

    PubMed

    Leighfield, Tod A; Muha, Noah; Ramsdell, John S

    2014-07-21

    Brevetoxins produced during algal blooms of the dinoflagellate Karenia are metabolized by shellfish into reduction, oxidation, and conjugation products. Brevetoxin metabolites comprising amino acid- and lipid conjugates account for a large proportion of the toxicity associated with the consumption of toxic shellfish. However, the disposition of these brevetoxin metabolites has not been established. Using intravenous exposure to C57BL/6 mice, we investigated the disposition in the body of three radiolabeled brevetoxin metabolites. Amino acid-brevetoxin conjugates represented by S-desoxy-BTX-B2 (cysteine-BTX-B) and lipid-brevetoxin conjugates represented by N-palmitoyl-S-desoxy-BTX-B2 were compared to dihydro-BTX-B. Tissue concentration profiles were unique to each of the brevetoxin metabolites tested, with dihydro-BTX-B being widely distributed to all tissues, S-desoxy-BTX-B2 concentrated in kidney, and N-palmitoyl-S-desoxy-BTX-B2 having the highest concentrations in spleen, liver, and lung. Elimination patterns were also unique: dihydro-BTX-B had a greater fecal versus urinary elimination, whereas urine was a more important elimination route for S-desoxy-BTX-B2, and N-palmitoyl-S-desoxy-BTX-B2 persisted in tissues and was eliminated equally in both urine and feces. The structures particular to each brevetoxin metabolite resulting from the reduction, amino acid conjugation, or fatty acid addition of BTX-B were likely responsible for these tissue-specific distributions and unique elimination patterns. These observed differences provide further insight into the contribution each brevetoxin metabolite class has to the observed potencies. PMID:24949875

  15. Quantification of ethanol methyl 1H magnetic resonance signal intensity following intravenous ethanol administration in primate brain

    PubMed Central

    Flory, Graham S.; O’Malley, Jean; Grant, Kathleen A.; Park, Byung; Kroenke, Christopher D.

    2009-01-01

    In vivo 1H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl 1H MRS signal intensity relates to tolerance to ethanol’s intoxicating effects. More recently, the ethanol 1H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T2 within these environments. The methods presented here extend ethanol MRS techniques to nonhuman primate subjects. Twelve monkeys were administered ethanol while sedated and positioned within a 3T MRI system. Chemical shift imaging (CSI) measurements were performed following intravenous infusion of 1g/kg ethanol. Magnetic resonance imaging (MRI) data were also recorded for each monkey to provide volume fractions of GM, WM, and CSF for each CSI spectrum. To estimate co-variance of ethanol MRS intensity with GM, WM, and CSF volume fractions, the relative contribution of each tissue subtype was determined following corrections for radiofrequency pulse profile non-uniformity, chemical shift artifacts, and differences between the point spread function in the CSI data and the imaging data. The ethanol MRS intensity per unit blood ethanol concentration was found to differ between GM, WM, and CSF. Individual differences in MRS intensity were larger in GM than WM. This methodology demonstrates the feasibility of ethanol MRS experiments and analysis in nonhuman primate subjects, and suggests GM may be a site of significant variation in ethanol MRS intensity between individuals. PMID:20018244

  16. Comparative Biodistribution and Pharmacokinetic Analysis of Cyclosporine-A in the Brain upon Intranasal or Intravenous Administration in an Oil-in-Water Nanoemulsion Formulation.

    PubMed

    Yadav, Sunita; Gattacceca, Florence; Panicucci, Riccardo; Amiji, Mansoor M

    2015-05-01

    The main objective of this study was to evaluate comparative biodistribution and pharmacokinetics of cyclosporine-A (CsA) following intranasal (IN) administration versus intravenous (IV) administration in Sprague-Dawley rats using an oil-in-water nanoemulsion delivery system. CsA, a hydrophobic peptide that is also a substrate for P-glycoprotein, is a well-known immunosuppressive agent. In the brain, CsA has been shown to be a potent anti-inflammatory and neuroprotective agent. CsA nanoemulsions (CsA-NE) and solution formulations (CsA-S) were prepared using an ultrasonication method and were characterized for drug content, encapsulation efficiency, globule size, and zeta potential. We compared the uptake of CsA-NE and CsA-S in brain regions and peripheral organs following IN and IV administration using LC-MS/MS based bioanalytical method. CsA-NE IN resulted in the highest accumulation compared to that with any other treatment and route of administration; this was consistent for all three regions of brain that were evaluated (olfactory bulbs, mid brain, and hind brain). The brain/blood exposure ratios of 4.49, 0.01, 0.33, and 0.03 for CsA-NE (IN), CsA-NE (IV), CsA-S (IN), and CsA-S (IV), respectively, indicated that CsA-NE is capable of direct nose-to-brain transport, bypassing the blood-brain barrier. Furthermore, CsA-NE administration reduces nontarget organ exposure. These studies show that IN delivery of CsA-NE is an effective way of brain targeting compared to that of other treatment strategies. This approach not only enhances the brain concentration of the peptide but also significantly limits peripheral exposure and the potential for off-target toxicity. PMID:25785492

  17. Pharmacokinetics and disposition of the novel dopamine agonist Z-7760 in rat after intravenous and oral administration.

    PubMed

    Bollard, M; Caldwell, J; Taylor, G W; Strolin-Benedetti, M; Semeraro, C

    2000-10-01

    1. Z-7760 (S(-)-N-[N-2-phenylethyl)-6-hexylamino]-N-propyl-5,6-dihydroxy-1,2,3,4-tetrahydro-2-naphthylamine dihydrobromide) is a potent dopamine D-1 and D-2 agonist synthesized during a search for agents to treat heart failure. Reported is the fate of the drug in rat. 2. 3H-Z-7760 was administered p.o. and i.v. to male Sprague-Dawley rats (0.4 mg and 400 microCi/kg in 0.1% ascorbic acid) and venous blood samples collected at intervals up to 48 h. Comparison of the AUC for total 3H showed that 37% of an oral dose of Z-7760 was absorbed. The percentage plasma 3H present as the parent compound fell from 82% 30 min after i.v. dosing to 12% after 24 h. After oral dosing, the fraction of plasma 3H present as unchanged Z-7760 was < 5% and this was essentially unaltered throughout the study. The long terminal elimination phase evident from 6 h was notable after both routes of administration. 3. The bile duct-cannulated rat was given 3H-Z-7760 p.o. (0.4 mg and 40 microCi/kg) and bile was collected for up to 22 h. Biliary excretion accounted for 30% of the dose. No parent compound was detected in the bile. 4. In further studies, other rats were dosed p.o. or i.v. with 3H-Z-7760 (0.4 mg and 400 microCi/kg) and urine and faeces were collected daily for 3 days. The major route of excretion was the faeces with 94-97% 3H recovered after oral and 70-73% after i.v. dosing. A further 4-7% was recovered in the urine after oral and 12-13% after i.v. dosing. 5. After oral administration of Z-7760 (100 mg/kg, 40 microCi/kg) to rats, the major metabolites in the urine were identified as the 5-O-methyl and glucuronic acid conjugates of Z-7760 by LC and MS. The glucuronide was only seen in urine after oral administration but 5-O-methyl-Z-7760 was present in urine and faeces after both routes of administration. 6. The low bioavailability of Z-7760 is the consequence of its poor absorption from the gastrointestinal tract as well as extensive first-pass metabolism that further reduces

  18. Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72. 3) in patients with carcinoma

    SciTech Connect

    Colcher, D.; Esteban, J.; Carrasquillo, J.A.; Sugarbaker, P.; Reynolds, J.C.; Bryant, G.; Larson, S.M.; Schlom, J.

    1987-08-01

    Monoclonal antibody (MAb) B72.3 has been shown to have selective reactivity for a wide range of carcinomas (colorectal, ovarian, breast, lung, gastric, and endometrial) versus normal adult tissues. /sup 131/I-Labeled B72.3 IgG has recently been shown to selectively bind carcinoma lesions when administered i.v. in patients with metastatic colorectal cancer. We report here the first direct comparison of i.p. administered (/sup 131/I)B72.3 IgG to specifically localize metastatic carcinoma. Three of 10 patients studied were negative for tumor detection by both CAT scan and X-ray but were positive for tumor localization via gamma scanning i.p. administered /sup 131/I-labeled MAb B72.3 IgG. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios of greater than 70:1 (based on percentage of injected dose/mg) for tumor MAb localization versus normal tissues. Specificity of (/sup 131/I)B72.3 tumor targeting was demonstrated by the concomitant administration of an equal dose of an /sup 125/I-labeled isotype identical (IgG1) control MAb. Simultaneous i.p. administration of (/sup 131/I)B72.3, and i.v. administration of (/sup 125/I)B72.3 in individual patients demonstrated: peritoneal implants are targeted more efficiently via i.p. MAb administration, and hematogenously spread and lymph node metastases as well as local recurrences are targeted more efficiently by i.v. administered MAb. No antibody toxicity was observed in any patients. Pharmacokinetics of MAb clearance demonstrated that only 10 to 30% of the i.p. administered MAb was found in plasma. These studies thus demonstrate the efficacy of intracavitary MAb administration as well as the advantage of the concomitant use of intracavitary and i.v. administered MAbs for tumor targeting and for potential MAb guided therapy of metastatic carcinoma.

  19. Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection.

    PubMed

    Wille, Timo; Neumaier, Katharina; Koller, Marianne; Ehinger, Christina; Aggarwal, Nidhi; Ashani, Yacov; Goldsmith, Moshe; Sussman, Joel L; Tawfik, Dan S; Thiermann, Horst; Worek, Franz

    2016-09-01

    The recent attacks with the nerve agent sarin in Syria reveal the necessity of effective countermeasures against highly toxic organophosphorus compounds. Multiple studies provide evidence that a rapid onset of antidotal therapy might be life-saving but current standard antidotal protocols comprising reactivators and competitive muscarinic antagonists show a limited efficacy for several nerve agents. We here set out to test the newly developed phosphotriesterase (PTE) mutant C23AL by intravenous (i.v.), intramuscular (i.m.; model for autoinjector) and intraosseous (i.o.; model for intraosseous insertion device) application in an in vivo guinea pig model after VX challenge (∼2LD50). C23AL showed a Cmax of 0.63μmolL(-1) after i.o. and i.v. administration of 2mgkg(-1) providing a stable plasma profile up to 180min experimental duration with 0.41 and 0.37μmolL(-1) respectively. The i.m. application of C23AL did not result in detectable plasma levels. All animals challenged with VX and subsequent i.o. or i.v. C23AL therapy survived although an in part substantial inhibition of erythrocyte, brain and diaphragm AChE was detected. Theoretical calculation of the time required to hydrolyze in vivo 96.75% of the toxic VX enantiomer is consistent with previous studies wherein similar activity of plasma containing catalytic scavengers of OPs resulted in non-lethal protection although accompanied with a variable severity of cholinergic symptoms. The relatively low C23AL plasma level observed immediately after its i.v. or i.o load, point at a possible volume of distribution greater than the guinea pig plasma content, and thus underlines the necessity of in vivo experiments in antidote research. In conclusion the i.o. application of PTE is efficient and resulted in comparable plasma levels to the i.v. application at a given time. Thus, i.o. vascular access systems could improve the post-exposure PTE therapy of nerve agent poisoning. PMID:27397758

  20. Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.

    PubMed

    Ueyama, Yukie; Lerche, Phillip; Eppler, C Mark; Muir, William W

    2009-12-01

    OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure. PMID:19951116

  1. A comparative study of the effects of the intravenous self-administration or subcutaneous minipump infusion of nicotine on the expression of brain neuronal nicotinic receptor subtypes.

    PubMed

    Moretti, Milena; Mugnaini, Manolo; Tessari, Michela; Zoli, Michele; Gaimarri, Annalisa; Manfredi, Irene; Pistillo, Francesco; Clementi, Francesco; Gotti, Cecilia

    2010-08-01

    Long-term nicotine exposure changes neuronal acetylcholine nicotinic receptor (nAChR) subtype expression in the brains of smokers and experimental animals. The aim of this study was to investigate nicotine-induced changes in nAChR expression in two models commonly used to describe the effects of nicotine in animals: operant (two-lever presses) intravenous self-administration (SA) and passive subcutaneous nicotine administration via an osmotic minipump (MP). In the MP group, alpha4beta2 nAChRs were up-regulated in all brain regions, alpha6beta2* nAChRs were down-regulated in the nucleus accumbens (NAc) and caudate-putamen, and alpha7 nAChRs were up-regulated in the caudal cerebral cortex (CCx); the up-regulation of alpha4beta2alpha5 nAChRs in the CCx was also suggested. In the SA group, alpha4beta2 up-regulation was lower and limited to the CCx and NAc; there were no detectable changes in alpha6beta2* or alpha7 nACRs. In the CCx of the MP rats, there was a close correlation between the increase in alpha4beta2 binding and alpha4 and beta2 subunit levels measured by means of Western blotting, demonstrating that the up-regulation was due to an increase in alpha4beta2 proteins. Western blotting also showed that the increase in the beta2 subunit exceeded that of the alpha4 subunit, suggesting that a change in alpha4beta2 stoichiometry may occur in vivo as has been shown in vitro. These results show that nicotine has an area-specific effect on receptor subtypes, regardless of its administration route, but the effect is quantitatively greater in the case of MP administration. PMID:20439469

  2. A 26-Week Toxicity Assessment of AIR001 (Sodium Nitrite) by Inhalation Exposure in Rats and by Intravenous Administration in Dogs.

    PubMed

    Tepper, Jeffrey; Ochoa, Ricardo; Rix, Peter; Elliott, Gary; Hoglen, Niel; Poulin, Dominic; Parsley, Ed; Masamune, Hiroko

    2014-05-01

    Historically, nitrogen oxides (NOx) in food, drinking water, as well as in the atmosphere have been believed to be associated with adverse health consequences. More recently, NOx have been implicated in normal homeostatic regulation, and exogenous administration has been associated with health benefits. One such potential health benefit is the prospect that inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation administration in rats and by intravenous infusion in dogs. The studies revealed that methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels less than 40% were well tolerated in both species, while levels greater than 50% methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated pharmacological effects occurred daily throughout the 26-week treatment period. Chronic exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in additional toxicity or compensatory responses. Based on the exposure levels that produced these pharmacodynamic responses in animals, relative to those measured in early clinical studies, it appears that an adequate margin of safety exists to support the continued clinical development of inhaled AIR001. PMID:24801488

  3. [Blood flow changes in the optic nerve head of albino rabbits following intravenous administration of brovincamine fumarate, an improver of cerebral circulation and metabolism].

    PubMed

    Nirei, M

    1996-02-01

    The blood flow changes in the optic nerve head in adult albino rabbits following intravenous administration of brovincamine fumarate, an improver of cerebral circulation and metabolism, were investigated employing the hydrogen clearance method. In the brovincamine fumarate (0.1 mg/kg)-administered group, the blood flow in the optic nerve head increased soon after injection and reached the maximal value of 124.2 +/- 7.3% against the value before injection, at 20 minutes after injection, followed by a gradual decrease in the blood flow. Statistical analysis showed a significant increase (p < 0.05) in the blood flow at 10 to 40 minutes after injection, compared with the value before injection in the brovincamine fumarate (0.1 mg/kg)-administered group, but no significant increases in the blood flow were observed in either the brovincamine fumarate (0.5 mg/kg)-administered group or the control group given no brovincamine fumarate throughout the course. No significant changes in the mean values of the blood pressure in the femoral artery, pulse rate, respiratory rate or rectal temperature were observed in any group through the experiment. To learn the mechanism of the different efficacy of the two doses, further studies are needed in light of the cyclic adenosine monophosphate (cyclic AMP) changes induced by brovincamine fumarate administration or in light of the receptor responsiveness to the drug concentration. PMID:8851150

  4. Case Report: Atrial Fibrillation After Intravenous Administration of Iodinated Contrast Medium in a Patient With Hepatocellular Carcinoma.

    PubMed

    Maimone, Sergio; Filomia, Roberto; Saitta, Carlo; Raimondo, Giovanni; Squadrito, Giovanni

    2015-09-01

    We describe the case of a 73-year-old woman with liver cirrhosis and hepatocellular carcinoma (HCC) who developed 2 distinct episodes of paroxystic atrial fibrillation (AF) each of which occurred 1 to 4 hours after iodine medium contrast-enhanced computed tomography. Sinus rhythm was restored by amiodarone therapy after the first AF episode and by electrical cardioversion after the second one. A careful clinical, biochemical, and instrumental examination showed that the patient had subclinical hyperthyroidism and moderate mitral insufficiency with mild atrial enlargement.Thus, the coexistence of both subclinical disthyroidism and of cardiac anatomical alterations may have predisposed the patient to AF that in fact occurred when exogenous iodine administration triggered a hyperthyroidism status. PMID:26334896

  5. Case Report: Atrial Fibrillation After Intravenous Administration of Iodinated Contrast Medium in a Patient With Hepatocellular Carcinoma

    PubMed Central

    Maimone, Sergio; Filomia, Roberto; Saitta, Carlo; Raimondo, Giovanni; Squadrito, Giovanni

    2015-01-01

    Abstract We describe the case of a 73-year-old woman with liver cirrhosis and hepatocellular carcinoma (HCC) who developed 2 distinct episodes of paroxystic atrial fibrillation (AF) each of which occurred 1 to 4 hours after iodine medium contrast-enhanced computed tomography. Sinus rhythm was restored by amiodarone therapy after the first AF episode and by electrical cardioversion after the second one. A careful clinical, biochemical, and instrumental examination showed that the patient had subclinical hyperthyroidism and moderate mitral insufficiency with mild atrial enlargement. Thus, the coexistence of both subclinical disthyroidism and of cardiac anatomical alterations may have predisposed the patient to AF that in fact occurred when exogenous iodine administration triggered a hyperthyroidism status. PMID:26334896

  6. Relation between respiratory function and pulmonary hemodynamics before and after intravenous administration of furosemide in acute myocardial infarction.

    PubMed

    Rolla, G; Bucca, C; Sclavo, M; Borello, G; Bellone, E

    1981-01-01

    Static lung volumes, flow volume curve in air and in a helium-oxygen mixture, PaO2 and pulmonary vascular pressures were measured in 16 patients 2 weeks after uncomplicated acute myocardial infarction and repeated 2 h after furosemide 40 mg i.v. administration. The patients with wedge pressure (WP) greater than 18 mm Hg had significantly lower values of FEV1, FEV1/VC%, MEF40 and MEF 25 in comparison with the patients with WE less than 18 mm Hg. A negative correlation was found between both PAP and WP and MEF25 values (p less than 0.001). After furosemide respiratory function tests improved only in patients with a good hemodynamic response to the drug. PaO2 did not change significantly. Airflow response to helium seemed to be a useful test for determining the site of major bronchial compression. PMID:7313341

  7. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    PubMed

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses. PMID:25274606

  8. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    PubMed

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug. PMID:18418357

  9. Clinical and economic evidence for intravenous acetaminophen.

    PubMed

    Yeh, Yu-Chen; Reddy, Prabashni

    2012-06-01

    Intravenous acetaminophen received United States Food and Drug Administration approval in November 2010 for the management of mild-to-moderate pain, management of moderate-to-severe pain with adjunctive opioid analgesics, and reduction of fever. Although intravenous acetaminophen generally improved pain relief and demonstrated opioid-sparing effects compared with placebo, it did not consistently reduce the frequency of opioid-related adverse events (e.g., postoperative nausea and vomiting). The safety and efficacy of intravenous acetaminophen as an antipyretic agent have been documented in adults and children; however, its cost is several-fold higher than that of the oral and rectal formulations. Although use of intravenous acetaminophen has reduced other postoperative resource utilization (e.g., hospital length of stay) in some studies outside the United States in patients undergoing abdominal surgery, a full economic evaluation in the United States has yet to be undertaken. In addition, its administration time (15-min infusion) and packaging (glass, single-use vial) have the potential to adversely affect patient flow in the postanesthesia care unit, create burden on patient care units, and lead to drug waste. Furthermore, 1 g of intravenous acetaminophen is formulated in 100 ml of solution, which may be an issue for patients with fluid restrictions. Given the clinical and economic evidence currently available, intravenous acetaminophen should not replace oral or rectal acetaminophen, but its use may be considered in a limited number of patients who cannot receive drugs orally and rectally and who cannot tolerate other parenteral nonopioid analgesic or antipyretic agents. PMID:22570116

  10. Pharmacokinetics of meloxicam in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections.

    PubMed

    Uney, Kamil; Altan, Feray; Aboubakr, Mohammed; Cetin, Gul; Dik, Burak

    2016-05-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam after single IV and IM injections in red-eared slider turtles (Trachemys scripta elegans). ANIMALS 8 healthy red-eared slider turtles. PROCEDURES Turtles received 1 dose of meloxicam (0.2 mg/kg) IV or IM (4 turtles/route), a 30-day washout period was provided, and then turtles received the same dose by the opposite route. Blood samples were collected at predetermined times for measurement of plasma meloxicam concentration. Pharmacokinetic values for each administration route were determined with a 2-compartment open model approach. RESULTS For IV administration, mean ± SD values of major pharmacokinetic variables were 1.02 ± 0.41 hours for distribution half-life, 9.78 ± 2.23 hours for elimination half-life, 215 ± 32 mL/kg for volume of distribution at steady state, 11.27 ± 1.44 μg•h/mL for area under the plasma concentration versus time curve, and 18.00 ± 2.32 mL/h/kg for total body clearance. For IM administration, mean values were 0.35 ± 0.06 hours for absorption half-life, 0.72 ± 0.06 μg/mL for peak plasma concentration, 1.5 ± 0.0 hours for time to peak concentration, 3.73 ± 2.41 hours for distribution half-life, 13.53 ± 1.95 hours for elimination half-life, 11.33 ± 0.92 μg•h/mL for area under the plasma concentration versus time curve, and 101 ± 6% for bioavailability. No adverse reactions were detected. CONCLUSIONS AND CLINICAL RELEVANCE Long half-life, high bioavailability, and lack of immediate adverse reactions of meloxicam administered IM at 0.2 mg/kg suggested the possibility of safe and effective clinical use in turtles. Additional studies are needed to establish appropriate administration frequency and clinical efficacy. PMID:27111010

  11. Cardiovascular effects of intravenous bolus administration and infusion of ketamine-midazolam in isoflurane-anesthetized dogs.

    PubMed

    Jacobson, J D; Hartsfield, S M

    1993-10-01

    Cardiovascular effects of IV administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and 6 dogs received K-M as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P < 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P < 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after K-M bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P < 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of K-M after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P < 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive K-M. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P < 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of K-M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8250398

  12. Intravenous conivaptan.

    PubMed

    Moen, Marit D; Keating, Gillian M

    2008-01-01

    *Conivaptan is an arginine vasopressin V1A and V2 receptor antagonist. The intravenous formulation is approved in the US for use in the treatment of euvolemic and hypervolemic hyponatremia. Conivaptan produces a dose-dependent electrolyte-sparing aquaresis (solute-free water excretion), increasing serum sodium levels. *In a randomized, double-blind, parallel-group, placebo-controlled, multicenter trial in adults with euvolemic or hypervolemic hyponatremia, the area under the serum sodium concentration-time curve over a 4-day treatment duration (primary endpoint) was significantly greater in intravenous conivaptan 40 mg/day recipients than in placebo recipients. *The total time during treatment that patients had serum sodium levels > or = 4 mEq/L above baseline was significantly longer in intravenous conivaptan than placebo recipients. In conivaptan recipients, an increase in serum sodium levels of > or = 4 mEq/L above baseline was achieved approximately 1 day after the first dose of the drug. *In addition, the mean change from baseline in free water clearance and effective water clearance over the first day of treatment was significantly greater with intravenous conivaptan than with placebo. *Given the nature of the treatment, the tolerability profile for intravenous conivaptan was generally acceptable in patients with hyponatremia. The most common adverse events were injection related (e.g. injection-site phlebitis), hypotension, and pyrexia. PMID:18828645

  13. Effect of intravenous administration of antioxidants alone and in combination on myocardial reperfusion injury in an experimental pig model

    PubMed Central

    Nikas, Dimitrios N.; Chatziathanasiou, Georgios; Kotsia, Anna; Papamichael, Nikos; Thomas, Christoforos; Papafaklis, Michail; Naka, Katerina K.; Kazakos, Nikos; Milionis, Haralampos J.; Vakalis, Kostas; Katsouras, Christos S.; Mpoumpa, Vasiliki; Vougiouklakis, Theodoros; Michalis, Lampros

    2008-01-01

    Background: Several antioxidants have been found to have conflicting results in attenuating myocardial reperfusion injury. These studies were done primarily in experimental protocols that did not approximate clinical situations. Objective: The aim of this study was to test the efficacy of 3 different antioxidants (ascorbic acid [AA], desferrioxamine, and N-acetylcysteine [NAC]) administered IV alone and in combination in a closed-chest pig model. Methods: Farm-raised domestic male pigs (aged 3–5 months, weight of 30–35 kg) were assigned to 1 of 5 groups to receive treatment as follows: group A, AA 100 mg/kg; group B, desferrioxamine 60 mg/kg; group C, a loading dose of NAC 100 mg/kg for 20 minutes and a 20-mg/kg maintenance dose; group D, all 3 drugs in combination; and group E, normal saline (control group). The infusion of all drugs was started 15 minutes before and completed 5 minutes after reperfusion, except for the administration of NAC, which was terminated 60 minutes postreperfusion. Myocardial ischemia (45 minutes) and reperfusion (210 minutes) were achieved percutaneously by circumflex artery balloon occlusion. Ejection fraction, left ventricular end-diastolic pressure (LVEDP), flow in the infarcted artery, and all ventricular arrhythmias were recorded. Oxidative stress was estimated by serial measurements of thiobarbituric acid reactive substance (TBARS) concentration in coronary sinus blood. Infarct size was assessed as a percentage of the area at risk (I/R ratio) using the tetrazolium red staining method. Results: The 25 pigs were divided into 5 groups of 5 pigs each. No significant between-group differences were found in I/R ratio or in oxidative stress (as measured by TBARS concentration). Group C developed significantly more ventricular atrhythmias than the control group (80% vs 0%, P = 0.02). No other differences among groups were found. LVEDP was significantly elevated in all treatment groups (mean LVEDP difference [SD] for group A, 6.0 [1

  14. Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

    PubMed

    Miao, Jingzhuo; Sun, Wanyang; Huang, Jingyi; Liu, Xiaolin; Li, Shuming; Han, Xiaoping; Tong, Ling; Sun, Guoxiang

    2016-09-01

    It is an essential requirement to clarify the metabolites of traditional Chinese medicine (TCM) injections, which contain numerous ingredients, to assess their safe and effective use in clinic. Salvianolic acid for injection (SAFI), made from hydrophilic phenolic acids in Salvia miltiorrhiza Bunge, has been widely used for the treatment of cerebrovascular diseases, but information on its metabolites in vivo is still lacking. In the present study, we aimed to holistically characterize the metabolites of the main active ingredients in rat plasma, bile, urine and feces following intravenous administration of SAFI. An ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was developed. Combining information on retention behaviors, multistage mass spectra and literature data, a total of eight prototypes and 52 metabolites were tentatively characterized. Metabolites originated from rosmarinic acid and salvianolic acid B comprised the majority of identified compounds. Meanwhile, four metabolites derived from salvianolic acid D and five from salvianolic acid B are reported for the first time. This study revealed that methylation, sulfation and glucuronidation were the major metabolic pathways of phenolic acids in SAFI in vivo. Furthermore, the developed UPLC/Q-TOF-MS method could also benefit the metabolic investigation of extracts and preparations in TCM with hydrophilic ingredients. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26910272

  15. Effect of the excipient concentration on the pharmacokinetics of PM181104, a novel antimicrobial thiazolyl cyclic peptide antibiotic, following intravenous administration to mice

    PubMed Central

    Yemparala, Vijayaphanikumar; Damre, Anagha A.; Manohar, Venkat; Sharan Singh, Kishori; Mahajan, Girish B.; Sawant, Satish N.; Deokule, Tanaji; Sivaramakrishnan, H.

    2014-01-01

    Thiazolyl cyclic peptide antibiotics are known for their poor aqueous solubility and unfavorable pharmacokinetics (PK) and hence pose challenging tasks in developing these antibiotics as clinical candidates. In the current paper, we report a possible way to address these challenges with exemplification of our antibiotic PM181104. The approach was to prepare formulations with known excipients, Polysorbate 80 (Tween 80, T-80) and PEG 400 through their varied stiochiometric combination in appropriate ratio to achieve acceptable osmolarity, pH and particle size of the formulation. Two different sets of formulations were prepared with two distinct average particle diameters ranging from 32.8 to 465.4 nm. First, semi-transparent solutions with a particle size of >100 nm were achieved by keeping concentration of PEG 400 constant at 8% (w/v) and decreasing the amounts of T-80. Second, clear colorless solutions with a particle size of <100 nm were achieved by keeping concentration of T-80 constant at 8% (w/v) and decreasing the amounts of PEG 400. In PK studies, intravenous administration of formulation with particle size <100 nm to mice resulted in a two-fold increase in area under the plasma concentration-time curve (AUClast) and concentration at time zero (C0), there by facilitating the selection of suitable formulation for further efficacy studies. PMID:25756005

  16. In vivo pharmacokinetics of and tissue distribution study of physalin B after intravenous administration in rats by liquid chromatography with tandem mass spectrometry.

    PubMed

    Zheng, Yunliang; Chen, Jing; Liu, Lin; Liang, Xingguang; Hong, Dongsheng

    2016-08-01

    A rapid and sensitive liquid chromatography tandem mass spectrometry quantitative analysis method was established for the pharmacokinetics and tissue distribution study of physalin B in rat. Physalin B and physalin H (internal standard, IS) were separated on an Agilent Eclips XDB C8 column. MS detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive eletrospray ionization source. The assay was validated in the concentration ranges of 22.6-22600 ng/mL for heart and lung and 4.52-4520 ng/mL for other tissues. The intra- and inter-day precisions (RSD) were ≤9.23 and ≤12.51%, respectively, with accuracy (%) in the range of 88.07-113.2%. A pharmacokinetic study showed that physalin B has a long dwell time with a half-life of 321.2 ± 29.5 min and clearance of 175.4 ± 25.7 mL/min/kg after intravenous administration. Additionally, physalin B showed a wide tissue distribution with a special higher penetration in lung. The data presented in this study could provide useful information for the further study of physalin B. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26714262

  17. Cytotoxic factor induced in murine serum after intravenous administration of a dehydrogenation polymer of p-coumaric acid (a synthetic lignin).

    PubMed

    Kohara, A; Shimizu, N; Kawazoe, Y

    1998-10-01

    A cytotoxic factor (CF) toward cultured murine leukemia L1210 cells was induced in mouse serum by intravenous injection of a dehydrogenation polymer of p-coumaric acid (DHP-pCA). When the serum from the treated mice was diluted with ethanol, CF was preserved in its supernatant (EtOH-sup). An EtOH-sup prepared from untreated control mice also showed cytotoxicity, although at much higher concentrations. The CF activity of EtOH-sups from both treated and untreated mice was completely eliminated by acid treatment at pH 2 at 90 degrees C for 30 min but kept intact by alkali treatment. In addition, the CF activity of both EtOH-sups was not affected by digestion with chymotrypsin. CF was recovered in a neutral MeOH-eluate from a DEAE-cellulofine column but not in HCI-MeOH eluate, in which lignified materials including DHP-pCA should have been recovered. These findings strongly suggest that CF is not a metabolite of DHP-pCA but an endogenous component of the normal serum which is augmented by DHP-pCA administration. PMID:9821818

  18. Intravenous administration of adipose tissue-derived stem cells enhances nerve healing and promotes BDNF expression via the TrkB signaling in a rat stroke model

    PubMed Central

    Li, Xin; Zheng, Wei; Bai, Hongying; Wang, Jin; Wei, Ruili; Wen, Hongtao; Ning, Hanbing

    2016-01-01

    Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs) transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF–TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO) rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats. PMID:27330296

  19. Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry.

    PubMed

    Ramakrishna, Rachumallu; Bhateria, Manisha; Singh, Rajbir; Puttrevu, Santosh Kumar; Bhatta, Rabi Sankar

    2016-06-01

    Agnuside (AGN), an iridoid glycoside, is the chemotaxonomic marker of the genus Vitex which has gained enormous attention by virtue of its potential health benefits. Regardless of claiming many therapeutic applications reports demonstrating its pharmacokinetics or quantification in biomatrices are lacking. This is the first report which presents a sensitive liquid chromatography coupled to a tandem mass spectrometry (LC-MS/MS) method for the quantification of AGN in mice plasma and various tissues (including liver, intestine, spleen, kidney, heart, lungs and brain). AGN was extracted from the biological samples using protein precipitation followed by liquid-liquid extraction and the separation was achieved on C18 reversed phase column with a mobile phase consisted of 0.1% formic acid in acetonitrile-0.1% formic acid in triple distilled water (92:8, v/v) at a flow rate of 0.7mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in negative scan mode. The bioanalytical method was found linear over the concentration range of 1-4000ng/mL for plasma and tissue homogenates (r(2)≥0.990). The lower limit of quantitation (LLOQ) for all matrices was 1ng/mL. Intra-day and inter-day variance and accuracy ranged from 90 to 110% and 1-10%, respectively. Matrix effect and recoveries were well within the satisfactory limits. The validated method was applied successfully to measure AGN concentrations in plasma and tissues following intravenous (i.v.) and peroral (p.o.) administration to mice. Maximal AGN concentrations in plasma and tissues were reached within 30-45min. The mean absolute bioavailability (%F) of AGN was∼0.7%. After oral administration, AGN was most abundant in intestine, followed by kidney, liver, spleen, brain, lungs and heart. The identified target tissues of AGN may help in understanding its pharmacological action in vivo. PMID:27018507

  20. Pharmacokinetic studies of phellodendrine in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Yi; Liu, Xin-Guang; Wang, Hui-Ying; Dong, Xin; Gao, Wen; Xu, Xiao-Jun; Li, Ping; Yang, Hua

    2016-09-01

    Phellodendrine, a quaternary ammonium alkaloid extracted from the dried bark of Phellodendrom chinensis Schneid and Phellodendrom amurense Rupr, has the effect of suppressing cellular immune response, reducing blood pressure and antinephritis. However, few investigations have been conducted for the pharmacokinetic study of phellodendrine. Thus, a rapid, simple and reliable ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ MS/MS) method has been established for quantification of phellodendrine in rat plasma and tissues by using magnoflorine as internal standard. The chromatographic separation was achieved on an Agilent ZORBAX SB-C18 column (4.6mm×50mm, 1.8μm) by gradient elution using 0.1% aqueous formic acid (A) and methanol (B). Triple quadrupole mass detection with multiple reaction monitoring mode was used to monitor the ion transitions, at m/z 342.20→192.20 for phellodendrine and m/z 342.20→58.20 for internal standard, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of phellodendrine after intravenous administration. The lower limits of quantification were 0.5ng/mL for plasma samples, 2.5ng/g for brain and 1ng/g for other tested tissues. Precisions and accuracy values were within the Food and Drug Administration acceptance criteria, the recovery and matrix effects were between 87.8-113.5%. The area under the curve (AUC0-t) ranged from 15.58 to 57.41mg/L min and Cmax were between 1.63-4.93mg/L. The results showed that phellodendrine was eliminated in 120min in plasma and most of tissues and the highest concentrations of phellodendrine were found in the kidney. This study may provide a basis for the further study of phellodendrine. PMID:27428451

  1. A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of escin Ia and escin Ib in human plasma: application to a pharmacokinetic study after intravenous administration.

    PubMed

    Liu, Lidong; Wu, Xiujun; Wu, Dan; Wang, Yingwu; Li, Pengfei; Sun, Yantong; Yang, Yan; Gu, Jingkai; Cui, Yimin

    2010-12-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of escin Ia and escin Ib in human plasma. After a solid-phase extraction (SPE), the analytes were separated on a Zorbax Extend C(18) column by isocratic elution with a mobile phase of methanol-acetonitrile-10 mm ammonium acetate (27:27:46, v/v/v) at a flow rate of 1.0 mL/min and analyzed by mass spectrometry in the positive ion multiple reaction monitoring mode. The precursor to product ion transitions of m/z 1131.8 → 807.6 was used to quantify escin Ia and escin Ib. Good linearity was achieved over a wide range of 2.00-900 ng/mL for escin Ia and 1.50-662 ng/mL for escin Ib. The intra- and inter-day precisions (as relative standard deviation) were less than 11% for each QC level of escin Ia and escin Ib. The accuracies (as relative error) were within ±5.27% for escin Ia and within ±4.07% for escin Ib. The method was successfully employed in a pharmacokinetic study after a single intravenous infusion administration of sodium aescinate injection containing 10 mg escin to each of the 10 healthy volunteers. PMID:20662111

  2. Intravenous ethanol increases dopamine release in the ventral striatum in humans: PET study using bolus-plus-infusion administration of [11C]raclopride

    PubMed Central

    Aalto, Sargo; Ingman, Kimmo; Alakurtti, Kati; Kaasinen, Valtteri; Virkkala, Jussi; Någren, Kjell; Rinne, Juha O; Scheinin, Harry

    2015-01-01

    Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [11C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [11C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40–50 minutes) and intervention (60–85 minutes) revealed an average 12.6% decrease in [11C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=−0.87, P=0.003) and putamen (r=−0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session. PMID:25492110

  3. Influenza viral load and peramivir kinetics after single administration and proposal of regimens for peramivir administration against resistant variants.

    PubMed

    Sato, Masatoki; Ito, Masaki; Suzuki, Shigeo; Sakuma, Hiroko; Takeyama, Aya; Oda, Shinichi; Watanabe, Masahiro; Hashimoto, Koichi; Miyazaki, Kyohei; Kawasaki, Yukihiko; Hosoya, Mitsuaki

    2015-03-01

    We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage. PMID:25547357

  4. Influenza Viral Load and Peramivir Kinetics after Single Administration and Proposal of Regimens for Peramivir Administration against Resistant Variants

    PubMed Central

    Ito, Masaki; Suzuki, Shigeo; Sakuma, Hiroko; Takeyama, Aya; Oda, Shinichi; Watanabe, Masahiro; Hashimoto, Koichi; Miyazaki, Kyohei; Kawasaki, Yukihiko; Hosoya, Mitsuaki

    2014-01-01

    We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage. PMID:25547357

  5. Plasma and ear tissue concentrations of enrofloxacin and its metabolite ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous administration of enrofloxacin.

    PubMed

    Cole, Lynette K; Papich, Mark G; Kwochka, Kenneth W; Hillier, Andrew; Smeak, Daniel D; Lehman, Amy M

    2009-02-01

    The purpose of this study was to measure the concentrations of enrofloxacin and its metabolite ciprofloxacin following intravenous administration of enrofloxacin in the plasma and ear tissue of dogs with chronic end-stage otitis undergoing a total ear canal ablation and lateral bulla osteotomy. The goals were to determine the relationship between the dose of enrofloxacin and the concentrations of enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin for treatment of chronic otitis externa and media. Thirty dogs were randomized to an enrofloxacin-treatment group (5, 10, 15 or 20 mg kg(-1)) or control group (no enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear canal, horizontal ear canal, middle ear) and a blood sample were collected. Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue were measured by high performance liquid chromatography. Repeated measures models were applied to log-transformed data to assess dosing trends and Pearson correlations were calculated to assess concentration associations. Ear tissue concentrations of enrofloxacin and ciprofloxacin were significantly (P < 0.05) higher than plasma concentrations. Each 5 mg kg(-1 )increase in the dose of enrofloxacin resulted in a 72% and 37% increase in enrofloxacin and ciprofloxacin concentrations, respectively. For bacteria with an minimal inhibitory concentration of 0.12-0.15 or less, 0.19-0.24, 0.31-0.39 and 0.51-0.64 microg mL(-1), enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg(-1), respectively. Treatment with enrofloxacin would not be recommended for a bacterial organism intermediate or resistant in susceptibility to enrofloxacin since appropriate levels of enrofloxacin would not be attained. PMID:19152587

  6. Simultaneous enantiomer determination of 20 (R)- and 20 (S)-ginsenoside-Rg2 in rat plasma after intravenous administration using HPLC method.

    PubMed

    Gui, Fang-Jin; Yang, Xiu-Wei; Li, Long-Yun; Tian, Jian-Ming

    2007-05-01

    20 (R,S)-Ginsenoside-Rg2, an anti-shock agent, is prescribed as a racemate. To analyze simultaneously the enantiomers of 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2 in plasma, a simple and reproducible high-performance liquid chromatographic (HPLC) method has been developed. The enantiomeric separation and determination were successfully achieved using a Diamonsil ODS C18 reversed-phase column (5 microm, 250 mm x 4.6 mm) with an RP18 (5 microm) guard column and a mobile phase of MeOH-aq. 4% H3PO4 (65:35, v/v, pH 5.1) with UV detection at 203 nm. Both enantiomers, 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2, were well separated at 14.5 min and 13.6 min, respectively. The linear ranges of the standard curves were 2.0-250 microg/ml. The intra- and inter-day precision (R.S.D.) were intravenous administration of 20 (R,S)-ginsenoside-Rg2. A pharmacokinetic study in rat plasma indicated that the enantiomers were rapidly absorbed and eliminated. These assay results are necessary for the evaluation of the metabolism of ginsenoside-Rg2 in vivo. PMID:17113840

  7. Intravenous Administration of Manuka Honey Inhibits Tumor Growth and Improves Host Survival When Used in Combination with Chemotherapy in a Melanoma Mouse Model

    PubMed Central

    Fernandez-Cabezudo, Maria J.; El-Kharrag, Rkia; Torab, Fawaz; Bashir, Ghada; George, Junu A.; El-Taji, Hakam; al-Ramadi, Basel K.

    2013-01-01

    Manuka honey has been recognized for its anti-bacterial and wound-healing activity but its potential antitumor effect is poorly studied despite the fact that it contains many antioxidant compounds. In this study, we investigated the antiproliferative activity of manuka honey on three different cancer cell lines, murine melanoma (B16.F1) and colorectal carcinoma (CT26) as well as human breast cancer (MCF-7) cells in vitro. The data demonstrate that manuka honey has potent anti-proliferative effect on all three cancer cell lines in a time- and dose-dependent manner, being effective at concentrations as low as 0.6% (w/v). This effect is mediated via the activation of a caspase 9-dependent apoptotic pathway, leading to the induction of caspase 3, reduced Bcl-2 expression, DNA fragmentation and cell death. Combination treatment of cancer cells with manuka and paclitaxel in vitro, however, revealed no evidence of a synergistic action on cancer cell proliferation. Furthermore, we utilized an in vivo syngeneic mouse melanoma model to assess the potential effect of intravenously-administered manuka honey, alone or in combination with paclitaxel, on the growth of established tumors. Our findings indicate that systemic administration of manuka honey was not associated with any alterations in haematological or clinical chemistry values in serum of treated mice, demonstrating its safety profile. Treatment with manuka honey alone resulted in about 33% inhibition of tumor growth, which correlated with histologically observable increase in tumor apoptosis. Although better control of tumor growth was observed in animals treated with paclitaxel alone or in combination with manuka honey (61% inhibition), a dramatic improvement in host survival was seen in the co-treatment group. This highlights a potentially novel role for manuka honey in alleviating chemotherapy-induced toxicity. PMID:23409104

  8. Disposition of Naltrexone after Intravenous Bolus Administration in Wistar Rats, Low-Alcohol-Drinking Rats and High-Alcohol-Drinking Rats

    PubMed Central

    Akala, Emmanuel O.; Wang, Hu; Adedoyin, Adedayo

    2010-01-01

    Reports have shown that interspecies differences in the metabolism and pharmacokinetics of naltrexone are a rule rather than exception. However, there is paucity of information on the disposition of naltrexone in selectively bred rat lines that reliably exhibit high and low voluntary alcohol consumption, and are often used to study alcohol-drinking behavior. We have characterized the pharmacokinetic profiles of naltrexone in selectively bred rat lines: high-alcohol-drinking (HAD-1) and low-alcohol-drinking (LAD-1) rats as well as the native Wistar strain. This study was carried out to establish a baseline pharmacokinetic profile of naltrexone in these rats prior to evaluating its pharmacokinetic profile in polymeric controlled-release formulations in our laboratory. The hypothesis is that alcohol-preferring and non-alcohol-preferring lines of rats should differ in the disposition of intravenously administered naltrexone. Naltrexone administration and blood collection were via the jugular vein. In a parallel experiment, naltrexone was administered via the jugular vein, but urine was collected using the Nalgene metabolic cage system. Data were analyzed by a noncompart-mental approach. Results show a high clearance that is close to or higher than hepatic blood flow in all groups (Wistar > LAD-1 > HAD-1, but with a statistically significant difference only between Wistar and HAD-1). Volume of distribution ( ~2.5-3 l/kg) and the half-life ( ~1 h) were similar. Urinary elimination of naltrexone was small, but also showed differences between the rats: HAD-1 > LAD-1 > Wistar, but with a statistically significant difference only between HAD-1 and Wistar rats. This study has therefore established the baseline disposition characteristics of naltrexone in these strains of rats. PMID:18832863

  9. Disposition of naltrexone after intravenous bolus administration in Wistar rats, low-alcohol-drinking rats and high-alcohol-drinking rats.

    PubMed

    Akala, Emmanuel O; Wang, Hu; Adedoyin, Adedayo

    2008-01-01

    Reports have shown that interspecies differences in the metabolism and pharmacokinetics of naltrexone are a rule rather than exception. However, there is paucity of information on the disposition of naltrexone in selectively bred rat lines that reliably exhibit high and low voluntary alcohol consumption, and are often used to study alcohol-drinking behavior. We have characterized the pharmacokinetic profiles of naltrexone in selectively bred rat lines: high-alcohol-drinking (HAD-1) and low-alcohol-drinking (LAD-1) rats as well as the native Wistar strain. This study was carried out to establish a baseline pharmacokinetic profile of naltrexone in these rats prior to evaluating its pharmacokinetic profile in polymeric controlled-release formulations in our laboratory. The hypothesis is that alcohol-preferring and non-alcohol-preferring lines of rats should differ in the disposition of intravenously administered naltrexone. Naltrexone administration and blood collection were via the jugular vein. In a parallel experiment, naltrexone was administered via the jugular vein, but urine was collected using the Nalgene metabolic cage system. Data were analyzed by a noncompartmental approach. Results show a high clearance that is close to or higher than hepatic blood flow in all groups (Wistar > LAD-1 > HAD-1, but with a statistically significant difference only between Wistar and HAD-1). Volume of distribution (approximately 2.5-3 l/kg) and the half-life (approximately 1 h) were similar. Urinary elimination of naltrexone was small, but also showed differences between the rats: HAD-1 > LAD-1 > Wistar, but with a statistically significant difference only between HAD-1 and Wistar rats. This study has therefore established the baseline disposition characteristics of naltrexone in these strains of rats. PMID:18832863

  10. Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self-administration during adulthood in male C57BL/6J mice.

    PubMed

    Dickson, Price E; Miller, Mellessa M; Rogers, Tiffany D; Blaha, Charles D; Mittleman, Guy

    2014-01-01

    Studies of adolescent drug use show (1) a pattern in which the use of tobacco precedes the use of other drugs and (2) a positive relationship between adolescent tobacco use and later drug use. These observations have led to the hypothesis that a causal relationship exists between early exposure to nicotine and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we tested the hypothesis that nicotine exposure in adolescence leads to increased intravenous self-administration (IVSA) of cocaine in adulthood. Using miniature osmotic pumps, we exposed mice and their littermate controls to nicotine (24 mg/kg/day) or vehicle, respectively, over the entire course of adolescence [postnatal days (P) 28-56]. Nicotine exposure was terminated on P56 and mice were not exposed to nicotine again during the experiment. On P73, mice were allowed to acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose-response curve was generated (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction conditions was also evaluated. All mice rapidly learned to lever press for the combination of cocaine infusions and non-drug stimuli. Analysis of the dose-response curve revealed that adolescent nicotine-exposed mice self-administered significantly more (P < 0.05) cocaine than controls at all but the highest dose. No significant differences were observed between adolescent nicotine-exposed and control mice during the acquisition or extinction stages. These results indicate that adolescent nicotine exposure can increase cocaine IVSA in mice, which suggests the possibility of a causal link between adolescent tobacco use and later cocaine use in humans. PMID:22978678

  11. Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration.

    PubMed

    Zimmermann, Estevan Sonego; Laureano, João Victor; Dos Santos, Camila Neris; Schmidt, Stephan; Lagishetty, Chakradhar V; de Castro, Whocely Victor; Dalla Costa, Teresa

    2015-01-01

    Levofloxacin (LEV) is a broad-spectrum fluoroquinolone used to treat pneumonia, urinary tract infections, chronic bacterial bronchitis, and prostatitis. Efflux transporters, primarily P-glycoprotein (P-gp), are involved in LEV's tissue penetration. In the present work, LEV free lung and prostate interstitial space fluid (ISF) concentrations were evaluated by microdialysis in Wistar rats after intravenous (i.v.) and intratracheal (i.t.) administration (7 mg/kg of body weight) with and without coadministration of the P-gp inhibitor tariquidar (TAR; 15 mg/kg administered i.v.). Plasma and tissue concentration/time profiles were evaluated by noncompartmental analysis (NCA) and population pharmacokinetics (popPK) analysis. The NCA showed significant differences in bioavailability (F) for the control group (0.4) and the TAR group (0.86) after i.t. administration. A four-compartment model simultaneously characterized total plasma and free lung (compartment 2) and prostate (compartment 3) ISF concentrations. Statistically significant differences in lung and prostate average ISF concentrations and levels of kidney active secretion in the TAR group from those measured for the control group (LEV alone) were observed. The estimated population means were as follows: volume of the central compartment (V1), 0.321 liters; total plasma clearance (CL), 0.220 liters/h; TAR plasma clearance (CLTAR), 0.180 liters/h. The intercompartmental distribution rate constants (K values) were as follows: K12, 8.826 h(-1); K21, 7.271 h(-1); K13, 0.047 h(-1); K31, 7.738 h(-1); K14, 0.908 h(-1); K41, 0.409 h(-1); K21 lung TAR (K21LTAR), 8.883 h(-1); K31 prostate TAR (K31PTAR), 4.377 h(-1). The presence of P-gp considerably impacted the active renal secretion of LEV but had only a minor impact on the efflux from the lung following intratracheal dosing. Our results strongly support the idea of a role of efflux transporters other than P-gp contributing to LEV's tissue penetration into the prostrate

  12. Quantification of cocaine and metabolites in exhaled breath by liquid chromatography-high-resolution mass spectrometry following controlled administration of intravenous cocaine.

    PubMed

    Ellefsen, Kayla N; Concheiro, Marta; Beck, Olof; Gorelick, David A; Pirard, Sandrine; Huestis, Marilyn A

    2014-10-01

    Breath has been investigated as an alternative matrix for detecting recent cocaine intake; however, there are no controlled cocaine administration studies that investigated the drug's disposition into breath. Breath was collected from 10 healthy adult cocaine users by asking them to breathe into a SensAbues device for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing on days 1, 5, and 10, and assayed with a validated liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6-126%, intra- and inter-assay imprecision was <10.6%, and bias was between -8.5 and 16.8%. No endogenous or exogenous interferences were observed for more than 75 tested. Analytes were generally stable under short-term storage conditions. Ion suppression was less than 46%. Of breath specimens collected after controlled cocaine administration, 2.6% were positive for cocaine (26.1-66 pg/filter, 1-9.5 h), 0.72% BE (83.3-151 pg/filter, 6.5-12.5 h), and 0.72% EME (50-69.1 pg/filter, 6.5-12.5 h); norcocaine was not detected. Methanolic extraction of the devices themselves, after filters were removed, yielded 19.2% positive cocaine tests (25.2-36.4 pg/device, 10 min-22 h) and 4.3% positive BE tests (26.4-93.7 pg/device, 10 min-22 h), explaining differences between the two extraction techniques. These results suggest that the device reflects the drug in oral fluid as well as lung microparticles, while the filter reflects only drug-laden microparticles. A sensitive and specific method for cocaine, BE, EME, and norcocaine quantification in breath was developed and validated. Cocaine in breath identifies recent cocaine ingestion, but its absence does not preclude recent use. PMID:25129634

  13. Pharmacokinetics and metabolism study of firocoxib in camels after intravenous administration by using high-resolution bench-top orbitrap mass spectrometry.

    PubMed

    Wasfi, Ibrahim A; Saeed, Hanan M; Agha, B A; Kamel, Asmaa M; Al Biriki, Nasreen A; Al Neaimi, Khaled M; Al Ali, Waleed A; Sultan, Saeed Mahmoud

    2015-01-01

    In this study, we developed a high-resolution liquid chromatography mass spectrometry method for the pharmacokinetic study of firocoxib followed by full method validation. Following a solid-phase extraction, the firocoxib and internal standard (celecoxib) were separated on an Agilent Zorbax ZDB C18 column (50 mm × 2.1 mm i.d., 3.5 μm) with a gradient elution using methanol and 0.1% aqueous formic acid. Data acquisition was performed at 25,000 resolution with the automatic gain set to 1,000,000 and the maximum injection time of 100 ms. Data were acquired in full-scan mode over a mass range of 100-550 Da in positive electrospray mode. Linear calibration curves were obtained over the concentration ranges of 0.5-200 ng/mL and no interfering peaks were detected at the retention time of firocoxib and internal standard in blank camel plasma samples. The mean extraction recoveries of firocoxib at three concentrations of 5, 25 and 75 ng/mL ranged from 92 to 104%. Coefficient of variation of intra-day and inter-day precision were both <10%. The accuracy of the method ranged from 95 to 107%. The validated method was then successfully applied in evaluating the pharmacokinetics and metabolism of firocoxib in camels (Camelus dromedarus) (n=5) following intravenous (i.v.) administration of a dose of 0.1 mgkg/body weight. The results obtained (mean ± SD) were as follows: the terminal elimination half-life (t₁/₂β) was 5.75 ± 2.26 h, and total body clearance (ClT) was 354.1 ± 82.6 mL/kg/h. The volume of distribution at steady state (VSS) was 2344.4 ± 238.7 mL/kg. One metabolite of firocoxib was tentatively identified as desalkyl firocoxib (m/z 283). Firocoxib could be detected in plasma 3-5 days following i.v. administration in camels using a sensitive liquid chromatography high-resolution orbitrap mass spectrometry method. PMID:25463193

  14. Efficacy and Safety of Single Low Dose Intravenous Fentanyl in Pain Reduction of Lumbar Puncture in Near Term Neonates by A Randomized Clinical Trial

    PubMed Central

    FALLAH, Razieh; HABIBIAN, Samaneh; NOORI-SHADKAM, Mahmood

    2016-01-01

    Objective Reduction of pain of invasive procedures in neonates can prevent pain side effects. The purpose of present study was to evaluate the efficacy and safety of a single low dose of intravenous fentanyl in reducing of lumbar puncture (LP) pain in neonates. Materials & Methods In this randomized clinical trial, registered with code number of 2014022616761N150, admitted neonates to Shahid Sadoughi Hospital, Yazd, Iran from August-April 2012 (45 cases) were randomly assigned into two groups to receive 2 μg/kg of intravenous fentanyl or 0.2 milliliter of normal saline, two min before LP. Primary outcome was success rate in reducing of pain during needle insertion to skin (pain score of less than three). Secondary outcomes were clinical side effects and serious adverse events. Results Forty-five neonates including 23 girls and 22 boys were evaluated. Pain reduction was obtained in 39.1% (9 of 23 neonates) of fentanyl group and in 4.5% (one of 22 neonates) of control group. Means of pulse rate (136.41± 9.16 vs. 148.9± 8.99) and pain score during needle insertion (3.41±1.31 vs. 5.8±1.12) were lower in fentanyl group. No severe adverse effects were seen in both groups. Side effects such as vomiting [9% (N=2) in control and 4.3% (N=1) in fentanyle group] and mild transient decrease in oxygen saturation in 8.7% (N=2) of fentanyle group were seen. Safety in two groups was not statistically different. Conclusion Intravenous fentanyl might be considered as a safe and effective analgesic drug in LP in neonates. PMID:27247585

  15. Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula.

    PubMed

    Li, Yueting; Lu, Yuan; Hu, Jianchun; Gong, Zipeng; Yang, Wu; Wang, Aimin; Zheng, Jiang; Liu, Ting; Chen, Tingting; Hu, Jie; Mi, Ling; Li, Yongjun; Lan, Yanyu; Wang, Yonglin

    2016-01-01

    Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats. Plasma samples were collected at various time points after a single dose (intravenous, i.v.) of Xin-Shao formula. The levels of plasma scutellarin and paeoniflorin at the designed time points were determined by a UPLC-MS/MS method, and drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. Increase in terminal elimination half-life (t1/2z) and mean residence time (MRT(0-t)) of scutellarin as well as elevation in area under the plasma drug concentration-time curve from 0 h to the terminal time point (AUC(0-t)) and maximum plasma drug concentration (Cmax) of paeoniflorin, along with decreased clearance of paeoniflorin and scutellarin as well as reduced apparent volume of distribution (Vz) of paeoniflorin, were observed in MCAO rats, compared with those in sham-operated animals. The elimination of scutellarin and paeoniflorin were reduced in cerebral I/R injury reduced rats. PMID:27617986

  16. 75 FR 62335 - Federal Housing Administration (FHA) Single Family Lender Insurance Process: Eligibility...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ... URBAN DEVELOPMENT 24 CFR Part 203 RIN 2502 AI58 Federal Housing Administration (FHA) Single Family....regulations.gov . FOR FURTHER INFORMATION CONTACT: Mark Ross, Acting Director, Office of Single Family Program... financing. FHA-insured single family mortgages are originated and underwritten through the...

  17. A prototype space flight intravenous injection system

    NASA Technical Reports Server (NTRS)

    Colombo, G. V.

    1985-01-01

    Medical emergencies, especially those resulting from accidents, frequently require the administration of intravenous fluids to replace lost body liquids. The development of a prototype space flight intravenous injection system is presented. The definition of requirements, injectable concentrates development, water polisher, reconstitution hardware development, administration hardware development, and prototype fabrication and testing are discussed.

  18. A study of pharmacokinetic interactions among co-existing ingredients in Viscum coloratum after intravenous administration of three different preparations to rats

    PubMed Central

    Ma, Yuying; Fan, Ronghua; Duan, Mengmeng; Yu, Zhiguo; Zhao, Yunli

    2015-01-01

    Background: Viscum coloratum (Komar) Nakai, known as Hujisheng in china, has been widely used as a herb medicine to treat a variety of diseases, including cardiovascular diseases, cancer, hypertension, hepatitis and hemorrhage. Objective: The aim was to investigate pharmacokinetic interactions among co-existing ingredients in V. coloratum after intravenous administration of three different preparations (four monomer solutions, the mixture of them and Viscum coloratum extracts) to rats. Materials and Methods: After protein precipitation pretreatment with plasma samples, high performance liquid chromatographic methods were developed and applied to quantitatively determinate the four components [syringin (Syri), homoeriodictyol-7-O-β-D-glycoside (Hedt-III), homoeriodictyol-7-O-β-D-apiose (1 → 2)-β-D-glycoside (Hedt-II) and homoeriodictyol-7-O-β-D-apiosiyl-(1 → 5)-β-D-apiosyl-(1 → 2)-β-D-glycoside (Hedt-I)]. The pharmacokinetic parameters (Area under the curve [AUC(0-t)], AUC(0-∞), t1/2) were calculated using DAS 2.1 software (Chinese Pharmacological Society, Shanghai, China) and compared statistically by One-way analysis of variance using SPSS software (18.0, Chicago, IL, USA) with P < 0.05 considered statistically significant. Results: Good linearities were achieved in the measured concentration range with R2 it0.9920. Precision, accuracy and extraction recovery were all within the acceptable range. For Syri, there was a significant difference only on t1/2 among three treatment groups. For Hedt-I, Hedt II and Hedt-III, three flavonoid glycosides, the change of AUC(0-t), AUC(0-∞) and t1/2 were markedly distinctive and even converse. Conclusion: Complex, extensive pharmacokinetic interactions were observed among these components in V. coloratum. They were mutually influenced by the in vivo absorption, distribution, metabolism and elimination. The result suggested traditional Chinese medicine was a complicated system, and we should take a scientific and

  19. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

    PubMed Central

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

  20. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia.

    PubMed

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

  1. Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

    PubMed

    Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

    2013-05-01

    Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

  2. Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens.

    PubMed

    Ji, L-W; Dong, L-L; Ji, H; Feng, X-W; Li, D; Ding, R-L; Jiang, S-X

    2014-06-01

    The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one-compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two-compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the Cmax (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration. PMID:24325541

  3. Pathology, organ distribution, and immune response after single and repeated intravenous injection of rats with clinical-grade parvovirus H1.

    PubMed

    Geletneky, Karsten; Leoni, Anne-Laure; Pohlmeyer-Esch, Gabriele; Loebhard, Stephanie; Baetz, Andrea; Leuchs, Barbara; Roscher, Mandy; Hoefer, Constance; Jochims, Karin; Dahm, Michael; Huber, Bernard; Rommelaere, Jean; Krebs, Ottheinz; Hajda, Jacek

    2015-02-01

    Parvovirus H1 (H1PV) is an autonomous parvovirus that is transmitted in rodent populations. Its natural host is rats. H1PV infection is nonpathogenic except in rat and hamster fetuses and newborns. H1PV infection of human cancer cells caused strong oncolytic effects in preclinical models. For a clinical trial of H1PV in patients with brain tumors, clinical-grade H1PV was produced according to Good Manufacturing Practices. This report focuses on results obtained after a single high-dose intravenous injection of highly purified H1PV in 30 rats and multiple (n = 17) intravenous injections at 3 dose levels in 223 rats. In both studies, no virus-related mortality or macroscopic organ changes related to H1PV occurred. Histopathology after multiple virus injections revealed minimal diffuse bile duct hyperplasia in livers of animals of the highest dose group and germinal center development in spleens of animals from the high-dose group. Liver changes were reversible within a 2-wk recovery period after the last injection. Hematology, blood chemistry, and coagulation analyses did not reveal significant toxicologic changes due to H1PV. Virus injection stimulated the production of IgG antibodies but did not alter mononuclear cell function or induce cytokine release. PCR analysis showed dose-dependent levels of viral genomes in all organs tested. The virus was excreted primarily through feces. These data provide important information regarding H1PV infection in its natural host. Due to the confirmation of the favorable safety profile of H1PV in a permissive animal model, a phase I/IIa clinical trial of H1PV in brain tumor patients could be initiated. PMID:25730754

  4. Potential resource and cost saving analysis of subcutaneous versus intravenous administration for rituximab in non-Hodgkin’s lymphoma and for trastuzumab in breast cancer in 17 Italian hospitals based on a systematic survey

    PubMed Central

    Ponzetti, Clemente; Canciani, Monica; Farina, Massimo; Era, Sara; Walzer, Stefan

    2016-01-01

    Introduction Subcutaneous versions of different oncology therapies have been available for patients for a few years, yet patient-relevant and hospital benefits have not been assessed in real life. Methods In order to analyze the impact of subcutaneous administrations for rituximab or trastuzumab in comparison to the respective intravenous mode a primary research in Italy was executed. The study’s primary objectives were to analyze the resource and cost implications from different perspectives (patient, medical staff) in the real world. The route of administration was discussed and aligned with the participating centers in order to capture all relevant therapy parts. After the successful execution of a pilot study 19 centers in six regions in Italy were recruited to participate. Results Significant time savings might be achieved with the subcutaneous mode through significantly lower patient preparation time including less time preparing the actual dosing for each individual patient. The total time difference is 3.3 hours with rituximab in hematology (non-Hodgkin’s lymphoma), which adds up to 23.55 hours for a full course of treatment per patient (overall preparation time: 40.1 hours intravenous [95% confidence interval (CI): ±0.47] vs 16.6 hours subcutaneous [95% CI: ±0.2]). In early breast cancer (trastuzumab), the time saving might be 3.3 hours for the first cycle and the total time saving for patient preparation might be 17.2 hours (overall preparation time: 38.8 hours intravenous [95% CI: ±9.42] vs 21.6 hours subcutaneous [95% CI: ±9.9]). Furthermore, in both settings, the time of medical staff was reduced and could hence be used elsewhere. Finally, in case wastage was experienced with intravenous therapies, there were potential significant reductions in wastage through the subcutaneous administration (93%–100%) with cost savings of €6,057 with rituximab subcutaneous and €28,399 with trastuzumab subcutaneous administration for the full treatment

  5. INTRAVENOUS ETHER ANESTHESIA

    PubMed Central

    Eger, Edmond I.; Johnson, Edward A.

    1963-01-01

    From a study of intravenous ether anesthesia, it was concluded that ether diluted to a 5 per cent solution in 5 per cent dextrose and water may be used to induce and maintain a smooth and easily controlled anesthetic state similar to that obtained with inhalation ether but without the dependence of the latter technique on ventilation. Cough and laryngospasm were absent. Adequate spontaneous respiration can be maintained with this technique. The technique is particularly useful in endoscopy during which the airway is often not available for anesthetic administration. PMID:14051486

  6. Pharmacokinetics of gentamicin following single-dose parenteral administration to goats.

    PubMed

    Garg, S K; Verma, S P; Uppal, R P

    1995-01-01

    The disposition kinetics of parenterally administered gentamicin (5 mg kg-1) has been studied in Gaddi goats. The serum concentration-time profile was described by bi-exponential and mono-exponential equations following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration with elimination half-life values of 0.96 +/- 0.09, 2.37 +/- 0.47 and 3.56 +/- 0.39 h, respectively. The apparent volume of distribution following i.v. administration (Vdarea: 0.26 +/- 0.041 kg-1) reflected limited extracellular distribution of the drug. The bioavailability was higher following i.m. administration (96.3%) compared to s.c. (76.9%). In view of the significantly longer biological half-life and larger area under the curve values, the s.c. route may be preferred. It is concluded that a suitable and practical dosage recommendation for gentamicin in goats would be 3.35 mg kg-1 body weight given s.c. at 12 h intervals. PMID:7552201

  7. [Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

    PubMed

    Raschka, C; Koch, H J

    2001-01-01

    We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks. PMID:11878089

  8. Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study.

    PubMed

    Dariane, Charles; Amin, Alexandre; Lortholary, Olivier; Lalli, Alexandre; Michel, Constance; Le Guilchet, Thomas; Treluyer, Jean-Marc; Nguyen-Khoa, Thao; De Toma, Claudia; Urien, Saïk; Méjean, Arnaud; Bourget, Philippe; Timsit, Marc-Olivier

    2016-08-01

    The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P < 0.001); median intraprostatic concentrations were 16.6 mg/L (95% CI 13.3-31.4 mg/L) and 4.2 mg/L (95% CI 3.1-4.9 mg/L), respectively (P < 0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P = 0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials. PMID:27324263

  9. Mask free intravenous 3D digital subtraction angiography (IV 3D-DSA) from a single C-arm acquisition

    NASA Astrophysics Data System (ADS)

    Li, Yinsheng; Niu, Kai; Yang, Pengfei; Aagaard-Kienitz, Beveley; Niemann, David B.; Ahmed, Azam S.; Strother, Charles; Chen, Guang-Hong

    2016-03-01

    Currently, clinical acquisition of IV 3D-DSA requires two separate scans: one mask scan without contrast medium and a filled scan with contrast injection. Having two separate scans adds radiation dose to the patient and increases the likelihood of suffering inadvertent patient motion induced mis-registration and the associated mis-registraion artifacts in IV 3D-DSA images. In this paper, a new technique, SMART-RECON is introduced to generate IV 3D-DSA images from a single Cone Beam CT (CBCT) acquisition to eliminate the mask scan. Potential benefits of eliminating mask scan would be: (1) both radiation dose and scan time can be reduced by a factor of 2; (2) intra-sweep motion can be eliminated; (3) inter-sweep motion can be mitigated. Numerical simulations were used to validate the algorithm in terms of contrast recoverability and the ability to mitigate limited view artifacts.

  10. Effects of dental treatment and single application of a 40% chlorhexidine varnish on mutans Streptococci in young children under intravenous anaesthesia.

    PubMed

    van Lunsen, D M; de Soet, J J; Weerheijm, K L; Groen, H J; Veerkamp, J S

    2000-01-01

    Clinical studies suggest that application of a highly concentrated chlorhexidine varnish results in a decrease in the number of mutans streptococci and thereby a decrease in the caries risks. The aim of this study was to determine the effect of dental treatment on the levels of mutans streptococci (MS) and lactobacilli (LB) and the additional effect of a single application of 40% chlorhexidine varnish (EC40) on the level of MS. Twenty-three children under the age of 5 years scheduled for full dental treatment were selected. Of these 23 children (mean dmf-s 27.1, SD 19.3), 11 children had nursing bottle caries. The mean sugar exposure was 6.4. Subjects were randomly distributed into two groups of approximately equal size. One group received an EC40 application after dental treatment, while the other group received only full dental treatment, both with intravenous anaesthesia with propofol as a single drug. An unstimulated saliva sample and a plaque sample were taken prior to dental treatment. The saliva and plaque sampling of the subjects was repeated after 6 weeks. MS and LB were isolated and counted. The number of children harbouring more than 10(6) MS in a pooled plaque sample decreased significantly from 8 to 2 children 6 weeks after dental treatment. No additional effect of EC40 was found. The number of salivary MS did not change significantly between the groups or before and after treatment. The figures for LB remained at a high level of more than 10(4)/ml saliva before (21 children) and 6 weeks after treatment (17 children). The results of this study indicate that dental treatment results in a significant suppression of plaque MS, while a single application of EC40 showed no significant additional suppression after 6 weeks. PMID:10867427

  11. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    SciTech Connect

    Waidyanatha, Suramya; Johnson, Jerry D.; Hong, S. Peter; Robinson, Veronica Godfrey; Gibbs, Seth; Graves, Steven W.; Hooth, Michelle J.; Smith, Cynthia S.

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  12. Nanosuspension formulations of poorly water-soluble compounds for intravenous administration in exploratory toxicity studies: in vitro and in vivo evaluation.

    PubMed

    Fujimura, Hisako; Komasaka, Takao; Tomari, Taizo; Kitano, Yasunori; Takekawa, Kouji

    2016-10-01

    This study was conducted to investigate the use of a nanosuspension for intravenous injection into dogs to increase exposure without toxic additives for preclinical studies in the discovery stage. Nanosuspensions were prepared with a mixer mill and zirconia beads with a vehicle of 2% (w/v) poloxamer 338, which was confirmed to lead to no histamine release in dogs. Sterilized nanosuspensions of poorly water-soluble compounds, cilostazol (Cil), spironolactone (Spi) and probucol (Pro), at 10 mg ml(-1) were obtained by milling for 30 min, followed by autoclaving for 20 min at 121 °C and milling for 30 min (mill-autoclave-mill method). The particle sizes (d50) of Cil, Spi and Pro were 0.554, 0.484 and 0.377 µm, respectively, and the percentages of the nominal concentration were 79.1%, 99.6% and 75.4%, respectively. In chromatographic data, no extra peaks were observed. The particle size of Cil was 0.564 µm after storage for 16 days at 2-8 °C. Cil in nanosuspension, but not in microsuspension, rapidly dissolved in dog plasma. Cil nanosuspension at 0.4 mg kg(-1) and Cil saline solution at 0.03 mg kg(-1) , around the saturation solubility, were intravenously administered to dogs. Nanosuspension increased exposure. The versatility of the mill-autoclave-mill method was checked for 15 compounds, and the particle size of 12 compounds was in the nano range. The nanosuspension optimized in this study may be useful for intravenous toxicological and pharmacological studies in the early stage of drug development. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26849104

  13. Does Intravenous Ketamine Enhance Analgesia after Arthroscopic Shoulder Surgery with Ultrasound Guided Single-Injection Interscalene Block?: A Randomized, Prospective, Double-Blind Trial

    PubMed Central

    2014-01-01

    Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and prevents pain associated with wind-up. We investigated whether low doses of ketamine infusion during general anesthesia combined with single-shot interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB. Forty adult patients scheduled for elective arthroscopic shoulder surgery were enrolled and randomized to either the control group or the ketamine group. All patients underwent SSISB and followed by general anesthesia. During an operation, intravenous ketamine was infused to the patients of ketamine group continuously. In control group, patients received normal saline in volumes equivalent to ketamine infusions. Pain score by numeric rating scale was similar between groups at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than 3 in both groups. The time to first analgesic request after admission on post-anesthesia care unit was also not significantly different between groups. Intraoperative low dose ketamine did not decrease acute postoperative pain after arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The preventive analgesic effect of ketamine could be mitigated by SSISB, which remains one of the most effective methods of pain relief after arthroscopic shoulder surgery. Graphical Abstract PMID:25045235

  14. XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind, placebo-controlled, dose-escalating study

    PubMed Central

    Deloche, Catherine; Lopez-Lazaro, Luis; Mouz, Sébastien; Perino, Julien; Abadie, Claire; Combette, Jean-Marc

    2014-01-01

    The aim of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of the JNK inhibitor XG-102 in a randomized, double blind, placebo controlled, sequential ascending dose parallel group Phase 1 Study. Three groups of male subjects received as randomly assigned ascending single XG-102 doses (10, 40, and 80 μg/kg; 6 subjects per dose) or placebo (2 subjects per dose) as an intravenous (IV) infusion over 60 min. Safety and tolerability were assessed by physical examination, vital signs, electrocardiography, eye examination, clinical laboratory tests and adverse events (AEs). PK was analyzed using noncompartmental methods. All reported AEs were mild to moderate and neither their number nor their distribution by System Organ Class suggest a dose relationship. Only headache and fatigue were considered probably or possibly study drug related. Headache frequency was similar for active and placebo, consequently this was not considered to be drug related but probably to study conditions. The other examinations did not show clinically relevant deviations or trends suggesting a XG-102 relationship. Geometric mean half-life was similar among doses, ranging from 0.36 to 0.65 h. Geometric mean XG-102 AUC0–last increased more than linearly with dose, 90% confidence intervals (CIs) did not overlap for the two highest doses. Geometric mean dose normalized Cmax values suggest a more than linear increase with dose but 90% CIs overlap. It may be concluded that XG-102 single IV doses of 10–80 μg/kg administered over 1 h to healthy male subjects were safe and well tolerated. PMID:25505576

  15. Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder.

    PubMed

    Enter, Dorien; Terburg, David; Harrewijn, Anita; Spinhoven, Philip; Roelofs, Karin

    2016-01-01

    Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially dominant gaze behavior. Therefore we tested as a proof of principle whether single dose testosterone administration can reduce gaze avoidance in SAD. In a double-blind, within-subject design, 18 medication-free female participants with SAD and 19 female healthy control participants received a single dose of 0.5mg testosterone and a matched placebo, at two separate days. On each day, their spontaneous gaze behavior was recorded using eye-tracking, while they looked at angry, happy, and neutral facial expressions. Testosterone enhanced the percentage of first fixations to the eye-region in participants with SAD compared to healthy controls. In addition, SAD patients' initial gaze avoidance in the placebo condition was associated with more severe social anxiety symptoms and this relation was no longer present after testosterone administration. These findings indicate that single dose testosterone administration can alleviate gaze avoidance in SAD. They support theories on the dominance enhancing effects of testosterone and extend those by showing that effects are particularly strong in individuals featured by socially submissive behavior. The finding that this core characteristic of SAD can be directly influenced by single dose testosterone administration calls for future inquiry into the clinical utility of testosterone in the treatment of SAD. PMID:26402923

  16. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    EPA Science Inventory

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
    Michael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas1
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  17. 78 FR 41075 - Federal Housing Administration (FHA): Single Family Quality Assurance-Solicitation of Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ... URBAN DEVELOPMENT Federal Housing Administration (FHA): Single Family Quality Assurance--Solicitation of Information on Quality Lending Practices AGENCY: Office of the Assistant Secretary for Housing--Federal... members of the public on ways to improve the efficiency and effectiveness of FHA's quality...

  18. Intracoronary versus intravenous high-dose bolus plus maintenance administration of tirofiban in patients undergoing primary percutaneous coronary intervention for acute ST elevation myocardial infarction.

    PubMed

    Candemir, Basar; Kilickap, Mustafa; Ozcan, Ozgur Ulas; Kaya, Cansin Tulunay; Gerede, Menekse; Ozdemir, Aydan Ongun; Ozdol, Cagdas; Kumbasar, Deniz; Erol, Cetin

    2012-07-01

    We aimed to examine whether intracoronary high-dose bolus of tirofiban plus maintenance would result in improved clinical outcome in STEMI patients undergoing primary PCI in this pilot trial. A total of 56 patients were enrolled to receive either intracoronary high-dose bolus plus maintenance (n = 34) or intravenous high-dose bolus plus maintenance (n = 22) of tirofiban. Pre and post intervention TIMI flow grades, myocardial blush grades, peak CKMB and troponin levels, time to peak CKMB and troponin, time to 50% ST resolution and major composite adverse cardiac event rates at 30 days were recorded. Although incidence of major adverse cardiac events was not different, post intervention TIMI flow and TIMI blush grades, peak CKMB and troponin levels, and time to peak CKMB and time to peak troponin were significantly different, favoring intracoronary strategy. In conclusion, this regimen improved myocardial reperfusion and coronary flow, and reduced myocardial necrosis, but failed to improve clinical outcomes at 30 days. PMID:22252901

  19. How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

    PubMed

    Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

    2015-03-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. PMID:25031222

  20. Safety of Ferric Carboxymaltose Immediately after Infliximab Administration, in a Single Session, in Inflammatory Bowel Disease Patients with Iron Deficiency: A Pilot Study

    PubMed Central

    Cortes, Xavier; Borrás-Blasco, Joaquín; Molés, Jose Ramón; Boscá, Maia; Cortés, Ernesto

    2015-01-01

    Aim To obtain preliminary safety and efficacy data on intravenous (IV) administration of infliximab (IFX) and ferric carboxymaltose (FCM) to inflammatory bowel disease (IBD) patients in a single treatment session. Methods A two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12) received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33) received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA) or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs) during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM) and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed. Results All 45 patients (35 Crohn´s disease, 10 ulcerative colitis) received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving. Conclusion Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single

  1. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    SciTech Connect

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.; Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel; Volk, David E.; Lokesh, Ganesh L.-R.; Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha; Rui, Hallgeir; Suh, K. Stephen; Gorenstein, David G.; Tanaka, Takemi

    2015-08-15

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

  2. Enterobacter sepsis in infants and children due to contaminated intravenous fluids.

    PubMed

    Matsaniotis, N S; Syriopoulou, V P; Theodoridou, M C; Tzanetou, K G; Mostrou, G I

    1984-10-01

    Sixty-three cases of nosocomial sepsis occurring from April through October 1981, in a 500-bed pediatric hospital, were traced to bacterial contamination of intravenous fluid produced by a single manufacturer. Two species of uncommon blood stream pathogens, Enterobacter cloacae and Enterobacter agglomerans contaminated the fluid. Infections with these organisms might have contributed to the death of four patients; two who were immunosuppressed, one who was asplenic and one premature infant. Epidemiologic and laboratory investigations identified the site of contamination to be within the screw-caps of the bottles containing the intravenous fluid. Contamination occurred during insertion of the intravenous fluid administration set into the bottle. The "epidemic" terminated when the hospital discontinued the use of infusion fluids from that manufacturer. We conclude that intravenous fluids should be examined during outbreaks of nosocomial bacteremia due to unusual pathogens. PMID:6567611

  3. Comparative electrocardiographic effects of intravenous ondansetron and granisetron in patients undergoing surgery for carcinoma breast: A prospective single-blind randomised trial

    PubMed Central

    Ganjare, Ashish; Kulkarni, Atul P

    2013-01-01

    Background: Postoperative nausea and vomiting (PONV) are common and distressing symptoms after surgery performed under general anaesthesia. 5-hydroxytryptamine3 antagonists are routinely used for prevention and treatment of PONV. The aim of our study was to compare the incidence of QTc prolongation and quantify the amount of QTc prolongation with ondansetron and granisetron. Methods: This prospective, randomised, single-blind study was carried out in the OT and Recovery Room (RR) of a tertiary referral cancer centre. After obtaining Institutional Review Board approval and written informed consent from the patients, 70 patients undergoing elective surgery for carcinoma breast were included. In the RR, patients randomly received 8 mg of ondansetron or 1 mg of granisetron intravenously. Serial ECGs were recorded at various intervals, Non-invasive blood pressure and SpO2 were also recorded. Chi-square test and Mann-Whiteny test were used for statistical analysis. Results: The demographics were similar in both groups. The incidence of significant QTc prolongation was significantly higher in the ondansetron group (22 of 37 (59.4%) vs. 11 of 33 patients (33.33%) (P<0.05)). There was an increase in the QTc interval in both the groups as compared to the baseline. The median prolongation in QTc interval from baseline was much more in the ondansetron group; this was statistically significant only at 5 and 15 min. Conclusion: Granisetron may be a safer option than ondanasetron for prevention and treatment of PONV due to lesser prolongation QTc interval. (ClinicalTrials.gov ID: NCT01352130) PMID:23716765

  4. The Effect of Administration of Ketamine and Paracetamol Versus Paracetamol Singly on Postoperative Pain, Nausea and Vomiting After Pediatric Adenotonsillectomy

    PubMed Central

    Kimiaei Asadi, Hosein; Nikooseresht, Mahshid; Noori, Lida; Behnoud, Fatholah

    2016-01-01

    Background: Tonsillectomy is one of the most common surgeries in children and posttonsillectomy pain and agitation management is a great challenge for anesthesiologists. Objectives: The aim of this study was to compare the efficacy of a single dose of ketamine combined with paracetamol with paracetamol alone in the management of postoperative pain in tonsillectomy. Materials and Methods: In this study, the subjects were randomly allocated into the two groups: the ketamine and control. Intravenous paracetamol infusion (15 mg/kg) was started 15 minutes before the end of surgery in both groups, continued with the IV injection of ketamine (0.25 mg/kg) in the ketamine group and an equal volume of saline in the control group. Using the children’s hospital of eastern Ontario (CHEOPS) pain scale, pain and agitation score and also the incidence of nausea and vomiting after the surgery were recorded in 0.5, 6 and 12 hours after the operation. Data were analyzed using SPSS software version 16 and P value less than 0.05 was considered as statistically significant in all cases. Results: There was no significant difference between the two groups considering demographic data (age, sex distribution, weight and height). The CHEOPS pain scales were significantly lower in the ketamine group compared to the control group at 0.5 and 6 hours after the surgery (P = 0.003 and P = 0.023, respectively). There was no significant difference in the CHEOPS scale at 12 hours after the surgery, dose of adjuvant analgesic and the incidence of nausea and vomiting after the surgery between the two groups. Conclusions: According to the results of the current study, postoperative analgesia in children was improved in the ketamine group. Therefore, for better management of posttonsillectomy pain, low-dose ketamine administration with paracetamol is recommended. PMID:27110529

  5. Disposition of bisphenol AF, a bisphenol A analogue, in hepatocytes in vitro and in male and female Harlan Sprague-Dawley rats and B6C3F1/N mice following oral and intravenous administration.

    PubMed

    Waidyanatha, Suramya; Mathews, James M; Patel, Purvi R; Black, Sherry R; Snyder, Rodney W; Fennell, Timothy R

    2015-01-01

    1. Bisphenol AF (BPAF) is used as a crosslinking agent for polymers and is being considered as a replacement for bisphenol A (BPA). 2. In this study, comparative clearance and metabolism of BPAF and BPA in hepatocytes and the disposition and metabolism of BPAF in rodents following oral administration of 3.4, 34 or 340 mg/kg [(14)C]BPAF were investigated. 3. BPAF was cleared more slowly than BPA in hepatocytes with the rate: rat > mouse > human. 4. [(14)C]BPAF was excreted primarily in feces by 72 h after oral administration to rats (65-80%) and mice (63-72%). Females excreted more in urine (rat, 15%; mouse, 24%) than males (rat, 1-4%; mouse, 10%). Residual tissue radioactivity was <2% of the dose at 72 h. Similar results were observed following intravenous administration. 5. In male rats, 52% of a 340 mg/kg oral dose was excreted in 24 h bile and was mostly comprised of BPAF glucuronide. However, >94% of fecal radioactivity was present as BPAF, suggesting extensive deconjugation in the intestine. 6. Metabolites identified in bile were BPAF-glucuronide, -diglucuronide, -glucuronide sulfate and -sulfate. 7. In conclusion, BPAF was well absorbed following gavage administration and highly metabolized and excreted mostly in the feces as BPAF. PMID:25923777

  6. Intravenous self-administration of etonitazene alone and combined with cocaine in rhesus monkeys: comparison with heroin and antagonism by naltrexone and naloxonazine

    PubMed Central

    Achat-Mendes, Cindy; Valdez, Glenn R.; Platt, Donna M.; Rowlett, James K.; Spealman, Roger D.

    2009-01-01

    Rationale In humans, μ opioid-cocaine combinations (speedballs) have been reported to heighten pleasurable effects and result in greater abuse potential compared to either drug individually. Emerging evidence in animals suggests that the ability of μ opioids to enhance the reinforcing effects of cocaine might be independent of their μ intrinsic efficacy even though μ agonist efficacy appears to be a determinant in the reinforcing effects of μ opioids themselves. Objectives This study examined the relationship between agonist efficacy, self-administration and the enhancement of cocaine self-administration using the high-efficacy μ agonist etonitazene. Methods Rhesus monkeys self-administered cocaine, heroin, etonitazene, and opioid-cocaine combinations under a progressive-ratio schedule of IV drug injection. Results Unlike cocaine and heroin, etonitazene did not maintain consistent self-administration at any dose tested (0.001 − 1.0 μg/kg/injection). However, combining etonitazene (0.1 − 1.0 μg/kg/inj) with cocaine (0.01 and 0.03 mg/kg/inj) enhanced cocaine self-administration, and this enhancement was attenuated by naltrexone. These effects are similar to those obtained by combining non-reinforcing doses of heroin and cocaine. Antagonism of etonitazene-cocaine and heroin-cocaine self-administration by naloxonazine was short-lasting and was not maintained after 24hrs (when naloxonazine's purported μ1 subtype antagonist effects are thought to predominate). Conclusions The results suggest that high μ agonist efficacy does not guarantee consistent drug self-administration and that the ability of μ agonists to enhance cocaine self-administration does not depend exclusively on reinforcing efficacy. Moreover, the results do not support a major role for μ1 receptor mechanisms in either etonitazene- or heroin induced enhancement of cocaine self-administration. PMID:19225763

  7. Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients.

    PubMed

    Menon, Anand G; Kuppen, Peter J K; van der Burg, Sjoerd H; Offringa, Rienk; Bonnet, Marie Claude; Harinck, Bert I J; Tollenaar, Rob A E M; Redeker, Anke; Putter, Hein; Moingeon, Philippe; Morreau, Hans; Melief, Cornelis J M; van de Velde, Cornelis J H

    2003-07-01

    Overexpression of p53 occurs in more than 50% of colorectal cancers. Therefore, p53 represents an attractive target antigen for immunotherapy. We assessed the safety of a canarypox virus encoding the human wild-type p53 gene given intravenously to end-stage colorectal cancer patients in a three-step dose escalation study aimed at inducing p53 immune responses. Patients with metastatic disease of p53-overexpressing colorectal cancers were vaccinated three times at 3-week intervals, each time with 10(6.5) CCID(50) (CCID(50)=cell culture infectious dose 50%; group 1, n=5), 10(7.0) CCID(50) (group 2, n=5) or 10(7.5) CCID(50) (group 3, n=6). Vital signs and the occurrence of adverse events were monitored and blood was analyzed for biochemical and hematological parameters as well as signs of auto-immune safety. In all, 16 patients were enrolled and 15 patients completed three vaccinations. No anaphylactic reaction or unwanted auto-immune reactions were observed. A total of 16 serious adverse events (SAEs) occurred: 10 in group 1, three in group 2 and three in group 3. All SAEs were tumor-related complications. There was no difference in the frequency of adverse events between the three groups, except for fever. Fever was the only vaccination-related adverse event consistently observed and was most frequent and outspoken in the group 3 patients. The majority was a grade 1 or 2 fever (93%) and grade 3 fever (7%) was observed in three patients of group 3. Some patients showed humoral and cellular responses against p53, following vaccinations. After having completed his initial treatment cycle, one patient (group 2) received a second treatment cycle of three doses of 10(7.5) CCID(50) and subsequently showed stable disease. All other patients showed progressive disease. We conclude that ALVAC-p53 can be administered intravenously to colorectal cancer patients without serious toxicity or pathological autoimmunity and can induce immune responses against p53. PMID:12833131

  8. Characterization of a cytotoxic factor induced in murine serum after the intravenous administration of dehydrogenation polymers of phenylpropenoids (a class of synthetic lignins).

    PubMed

    Shimizu, N; Kohara, A; Kawazoe, Y

    1997-08-01

    A cytotoxic factor (CF) appeared in murine serum after the intravenous injection of the dehydrogenation polymers (DHPs) of p-coumaric acid (DHP-pCA), caffeic acid (DHP-CA), and ferulic acid (DHP-FA), which are categorized as a class of synthetic lignins. The highest CF activity was observed 15 min after the i.v. injection of DHP-pCA. CF is likely to be cytocidal through an apoptotic mechanism accompanied by nucleosome-sized DNA fragmentation. CF is extractable with aqueous ethanol and highly stable against heat, proteases, and acid/alkali treatments. The ethanol extract showed cytotoxicity toward various cultured cell lines and also ascites carcinoma cells in vivo. The parent molecules DHPs did not show any appreciable cytotoxicity. After the induction of CF activity, the activity quickly diminished and completely disappeared from the blood stream within an hour or so. The cytotoxicity was observed only when the target cells were exposed to CF for longer than 10 h. PMID:9300127

  9. Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene.

    PubMed

    Uin, Gan Shu; Maria, Notaridou; Ying, Fu Zhen; Kok Onn, Lee; Chuan, Sia Kian; Chunilal, Nathwani Amit; Marco, Della Peruta; Yorke, Calne Roy

    2016-01-01

    We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients. PMID:26795016

  10. PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases

    PubMed Central

    Kaminskas, Lisa M; Ascher, David B; McLeod, Victoria M; Herold, Marco J; Le, Caroline P; Sloan, Erica K; Porter, Christopher JH

    2014-01-01

    The efficacy of protein-based therapeutics with indications in the treatment of lymphatic diseases is expected to be improved by enhancing lymphatic disposition. This study was therefore aimed at examining whether PEGylation can usefully be applied to improve the lymphatic uptake of interferon α2 and whether this ultimately translates into improved therapeutic efficacy against lymph-resident cancer. The lymphatic pharmacokinetics of interferon α2b (IFN, 19 kDa) and PEGylated interferon α2b (IFN-PEG12, 31 kDa) or α2a (IFN-PEG40, 60 kDa) was examined in thoracic lymph duct cannulated rats. IFN was poorly absorbed from the SC injection site (Fabs 36%) and showed little uptake into lymph after SC or IV administration (≤1%). In contrast, IFN-PEG12 was efficiently absorbed from the SC injection site (Fabs 82%) and approximately 20% and 8% of the injected dose was recovered in thoracic lymph over 30 hours after SC or IV administration respectively. IFN-PEG40, however, was incompletely absorbed from the SC injection site (Fabs 23%) and showed similar lymphatic access after SC administration to IFN-PEG12 (21%). The recovery of IFN-PEG40 in thoracic lymph after IV administration, however, was significantly greater (29%) when compared to IV IFN-PEG12. The anti-tumour efficacy of interferon against axillary metastases of a highly lymph-metastatic variant of human breast MDA-MB-231 carcinoma was significantly increased by SC administration of lymph-targeted IFN-PEG12 when compared to the administration of IFN on the ipsilateral side to the axillary metastasis. Optimal PEGylation may therefore represent a viable approach to improving the lymphatic disposition and efficacy of therapeutic proteins against lymphatic diseases. PMID:23499718

  11. A Single Intraduodenal Administration of Human Adenovirus 40 Vaccine Effectively Prevents Anaphylactic Shock

    PubMed Central

    Yamasaki, Satoshi; Miura, Yoshiaki; Davydova, Julia; Vickers, Selwyn M.

    2013-01-01

    Vaccine administration into the intestine is known to induce mucosal tolerance most efficiently. Therefore, developing a delivery system that targets the intestinal mucosa is expected to improve the efficiency of immunosuppression. Human enteric adenovirus serotype 40 (Ad40)-based vectors have the advantage of targeting intestinal mucosa, making them prime candidates as mucosal vaccine carriers for immunosuppression. Here, after both oral and intraduodenal administrations, the vector distribution of replication-defective recombinant Ad40 vectors (rAd40) was significantly higher than that of a conventional Ad vector based on human adenovirus 5 (Ad5) in ilea containing Peyer's patches. Single intraduodenal administration of rAd40 induced antigen-specific mucosal immunoreaction mediated by intestinal mucosal and systemic immunity. In ovalbumin-induced allergy mouse models, this approach inhibited antigen-specific delayed-type hypersensitivity reactions, diarrhea occurrence, and systemic anaphylaxis. Thus, a single intraduodenal administration of rAd40 provides a potent method of inducing allergen-specific mucosal tolerance and a new allergen-specific immunotherapy for overcoming problems with current therapies against life-threatening allergic reactions, including anaphylaxis. PMID:23885027

  12. Efficacy of two-time prophylactic intravenous administration of tazobactam/piperacillin for transrectal ultrasound-guided needle biopsy of the prostate

    PubMed Central

    Iwamoto, Hiroaki; Shigehara, Kazuyoshi; Miyagi, Tohru; Nakashima, Takao; Shimamura, Masayoshi; Namiki, Mikio

    2015-01-01

    Background Prevalence of fluoroquinolone (FQ)-resistant Escherichia coli has been recently increasing worldwide. We analyzed the incidence and characteristics of acute bacterial prostatitis after transrectal ultrasound-guided needle prostate biopsy (TRUSP-Bx) with prophylactic tazobactam/piperacillin (TAZ/PIPC) treatment as an alternative regimen. Methods A total of 391 patients who underwent TRUSP-Bx were included in the study. All patients received intravenous TAZ/PIPC (4.5 g) 30 minutes before and 6 hours after TRUSP-Bx. Results Acute bacterial prostatitis developed in six patients (1.5%); the frequency of its occurrence was significantly higher in patients in whom rectal disinfection was not performed (P < 0.05). These six patients developed clinical symptoms of acute bacterial prostatitis a median of 24 hours after the biopsy. Escherichia coli was isolated in urine or blood bacterial cultures in four cases, and Klebsiella pneumoniae in two cases. All of the isolated organisms showed excellent sensitivity to TAZ/PIPC. Conclusions The incidence rate of acute prostatitis with prophylactic TAZ/PIPC was consistent with those reported previously with FQ-based regimens, despite the favorable sensitivity of isolated organisms. Two-time regimen of TAZ/PIPC may not always prevent the post-TRUSP-Bx infection, possibly due to the pharmacokinetic characteristics of TAZ/PIPC. However, if each case was considered individually to select the best setting and frequency of dosage of TAZ/PIPC, this can be an optimal prophylaxis in the era of widespread FQ-resistant microorganisms. PMID:26473153

  13. Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration.

    PubMed

    Cimmino, Giovanni; Giannarelli, Chiara; Chen, Wei; Alique, Matilde; Santos-Gallego, Carlos G; Fuster, Valentin; Hajjar, Roger J; Walsh, Christopher E; Badimon, Juan J

    2011-03-01

    Apolipoprotein A-I (ApoA-I)/high-density lipoprotein (HDL)-raising treatments are effective antiatherosclerotic strategies. We have compared the antiatherogenic effects of human ApoA-I (hApoA-I) overexpression by intraportal and intramuscular gene transfer in atherosclerotic ApoE-knockout mice. Atherosclerotic lesions were induced by atherogenic diet. After atherosclerosis induction, a group of animals was killed and served as atherosclerosis baseline-control group. The remaining animals were randomized into the following groups: (1) atherosclerosis-progression-control, (2) intraportal/vector administration, and (3) intramuscular/vector administration. Aortas and hearts were processed for atherosclerotic quantification by en face Sudan IV and Oil Red-O, respectively. Liver and muscle specimens were processed for protein/gene expression analysis. A sustained increase in hApoA-I/HDL plasma levels was observed in both transduced groups. hApoA-I overexpression abolished plaque progression versus progression-control group. hApoA-I overexpression significantly reduced lesion macrophage, feature indicative of plaque stabilization. Scavenger receptor class-B type I (SR-BI), but not ATP-binding cassette, sub-family A (ABCA), member 1 (ABCA-1), was significantly upregulated in treated groups versus progression-controls. The results of this study show a similar effect of hApoA-I/HDL overexpression on plaque progression/stabilization by 2 different routes of administration. Our results showing similar effects using either intramuscular administration and intraportal route of administration may have significant clinical implications, given the reduced medical risk to patient and cost of intramuscular injections. PMID:21164355

  14. Intra-arterial administration of recombinant tissue-type plasminogen activator (rt-PA) causes more intracranial bleeding than does intravenous rt-PA in a transient rat middle cerebral artery occlusion model

    PubMed Central

    2011-01-01

    Background Intra-arterial (IA) administration of rt-PA for ischemic stroke has the potential for greater thrombolytic efficacy, especially for a large thrombus in the M1 or M2 segment of the middle cerebral artery (MCA). Intracranial hemorrhage (ICH) is a concern with IA or intravenous (IV) administration especially as the therapeutic window is extended. However, because IA administration delivers a higher local concentration of agent, the incidence and severity of ICH may be greater than with similar doses IV. We investigated the safety of rt-PA administration by IA compared to IV infusion following 6 hours of MCA occlusion (MCAo) with reflow in the spontaneously hypertensive rat (SHR). Methods Male SHRs were subjected to 6 hours MCAo with 18 hours reflow using a snare ligature model. They were treated with IA saline, IA rt-PA (1, 5, 10, 30 mg/kg), or IV rt-PA (10 and 30 mg/kg) by a 10 to 60 minute infusion beginning approximately 1 minute before reflow. The rats were recovered for 24 hours after MCAo onset at which time Bleeding Score, infarct volume, and Modified Bederson Score were measured. Results Greater hemorrhagic transformation occurred with 10 and 30 mg/kg rt-PA administered IA than IV. The IV 10 mg/kg rt-PA dosage induced significantly less bleeding than did the 1 or 5 mg/kg IA groups. No significant increase in infarct volume was observed after IA or IV treatment. Rats treated with 30 mg/kg rt-PA by either the IA or IV route had greater neurological dysfunction compared to all other groups. Conclusions Administration of rt-PA by the IA route following 6 hours of MCAo results in greater ICH and worse functional recovery than comparable dosages IV. Significantly greater bleeding was observed when the IA dose was a tenth of the IV dose. The increased bleeding did not translate in larger infarct volumes. PMID:21933438

  15. Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors

    SciTech Connect

    Huebler, Nicole; Gottschling, Barbara . E-mail: barbara.gottschling@merck.de; Jacobs, Maren; Landenberg, Friedrich von; Hewicker-Trautwein, Marion

    2005-11-01

    Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

  16. Intravenous Cocaine Induces Rapid, Transient Excitation of Striatal Neurons via its Action on Peripheral Neural Elements: Single-cell, Iontophoretic Study in Awake and Anesthetized Rats

    PubMed Central

    Kiyatkin, Eugene A.; Brown, Paul Leon

    2007-01-01

    Cocaine’s (COC) direct interaction with the dopamine (DA) transporter is usually considered the most important action underlying the psychomotor stimulant and reinforcing effects of this drug. However, some physiological, behavioral and psycho-emotional effects of COC are very rapid and brief and they remain intact during DA receptor blockade, suggesting possible involvement of peripheral non-DA neural mechanisms. To assess this issue, single-unit recording with microiontophoresis was used to examine changes in impulse activity of dorsal and ventral striatal neurons to intravenous (iv) COC (0.25–0.5 mg/kg) in the same rats under two conditions: awake with dopamine (DA) receptor blockade and anesthetized with urethane. In the awake preparation ~70% striatal neurons showed rapid and transient (latency ~ 6 s, duration ~15 s) COC-induced excitations. These effects were stronger in ventral than dorsal striatum. During anesthesia, these phasic effects were fully blocked and COC slowly decreased neuronal discharge rate. COC-methiodide (COC-M), a derivative that cannot cross the blood-brain barrier, also caused phasic excitations in the awake, but not anesthetized condition. In contrast to regular COC, COC-M had no tonic effect on discharge rate in either preparation. Most striatal neurons that were phasically excited by both COC forms also showed short-latency excitations during tail-touch and tail-pinch in the awake preparation, an effect strongly attenuated during anesthesia. Finally, most striatal neurons that in awake conditions were phasically excited by somato-sensory stimuli and COC salts were also excited by iontophoretic glutamate (GLU). Although striatal neurons were sensitive to GLU in both preparations, the response magnitude at the same GLU current was higher in awake than anesthetized conditions. These data suggest that in awake animals iv COC, like somato-sensory stimuli, transiently excites striatal neurons via its action on peripheral neural elements

  17. Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cells Induces a Switch from Classical to Atypical Symptoms in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Kurte, Mónica; Bravo-Alegría, Javiera; Torres, Alexander; Carrasco, Vania; Ibáñez, Cristina; Vega-Letter, Ana María; Fernández-O'Ryan, Catalina; Irarrázabal, Carlos E.; Figueroa, Fernando E.; Fuentealba, Rodrigo A.; Riedel, Claudia; Carrión, Flavio

    2015-01-01

    Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis. PMID:25838828

  18. Pharmacokinetic Profile and Acute Toxicological Properties of a Novel Radiosensitizer Cytosine-Phosphate-Guanosine Oligodeoxynucleotide 107 in Mice Following Intravenous and Orthotopic Administration.

    PubMed

    Cen, Yanyan; Li, Xiaoli; Yin, Zhiwei; Yan, Zifei; Liu, Dan; Peng, Wei; Pan, Feng; Zhou, Hong

    2015-10-01

    The synthetic cytosine-phosphate-guanosine oligodeoxynucleotide 107 (CpG ODN107) is a novel radiosensitizer for glioma treatment. However, the information related to its pharmacokinetics and toxicity remains unclear. Therefore, the plasma pharmacokinetics, distribution, elimination, and acute toxicity of CpG ODN107 in mice were investigated in the present experiments. The results from the liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay showed that the plasma elimination half-life (t1/2β) of CpG ODN107 in BALB/c mice varied slightly with the dose, and it was 0.65, 0.49, and 0.50 h at the intravenous doses of 2.5, 5, and 10 mg/kg, respectively. CpG ODN107 rapidly and widely distributed in organs/tissues, except the brain and testes. The highest concentrations were found in the liver (28.6% of the administered dose after 0.5 h) and the kidneys (5.7% of the administered dose after 1 h). CpG ODN107 (0.3, 3, and 30 μg/mL) could highly bind to human and mouse plasma proteins in vitro. CpG ODN107 in the forms of prototype was excreted in urine (1.79%) and feces (0.91%), and its shortened metabolites were excreted in urine (2.1%) and feces (2.2%) within the first 24 h. The mice in vivo optical image showed CpG ODN107 labeled with Alexa Fluor 680 fluorochrome (AF680) accumulated in the brain after orthotopic injection, eliminated very slowly, and excreted in urine compared with poly T labeled with AF680. The median lethal dose (LD50) of CpG ODN107 was 75.7 mg/kg for mice; this dose only could produce apparent spleen and liver damage, in line with the distribution features of CpG ODN. In conclusion, our present pharmacokinetic and toxicity investigation will provide helpful information to further pharmacodynamic and pharmacokinetic research of CpG ODN107 and other oligodeoxynucleotide drugs in the future. PMID:26213852

  19. A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

    PubMed Central

    Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A.; Muñoz, Manuel

    2016-01-01

    Background Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. Materials and methods From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Results Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Discussion Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID:26674819

  20. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    PubMed

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate. PMID:24419513

  1. Effects of intraoperative single bolus fentanyl administration and remifentanil infusion on postoperative nausea and vomiting

    PubMed Central

    Lim, Hyungsun; Doo, A Ram; Son, Ji-Seon; Kim, Jin-Wan; Lee, Ki-Jae; Kim, Dong-Chan

    2016-01-01

    Background Although the use of postoperative opioids is a well-known risk factor for postoperative nausea and vomiting (PONV), few studies have been performed on the effects of intraoperative opioids on PONV. We examined the effects of a single bolus administration of fentanyl during anesthesia induction and the intraoperative infusion of remifentanil on PONV. Methods Two hundred and fifty women, aged 20 to 65 years and scheduled for thyroidectomy, were allocated to a control group (Group C), a single bolus administration of fentanyl 2 µg/kg during anesthesia induction (Group F), or 2 ng/ ml of effect-site concentration-controlled intraoperative infusion of remifentanil (Group R) groups. Anesthesia was maintained with sevoflurane and 50% N2O. The incidence and severity of PONV and use of rescue antiemetics were recorded at 2, 6, and 24 h postoperatively. Results Group F showed higher incidences of nausea (60/82, 73% vs. 38/77, 49%; P = 0.008), vomiting (40/82, 49% vs. 23/77 30%; P = 0.041) and the use of rescue antiemetics (47/82, 57% vs. 29/77, 38%; P = 0.044) compared with Group C at postoperative 24 h. However, there were no significant differences in the incidence of PONV between Groups C and R. The overall incidences of PONV for postoperative 24 h were 49%, 73%, and 59% in Groups C, F, and R, respectively (P = 0.008). Conclusions A single bolus administration of fentanyl 2 µg/kg during anesthesia induction increases the incidence of PONV, but intraoperative remifentanil infusion with 2 ng/ml effect-site concentration did not affect the incidence of PONV. PMID:26885302

  2. Distribution and analgesia of [3H][D-Pen2, D-Pen5]enkephalin and two halogenated analogs after intravenous administration.

    PubMed

    Weber, S J; Greene, D L; Sharma, S D; Yamamura, H I; Kramer, T H; Burks, T F; Hruby, V J; Hersh, L B; Davis, T P

    1991-12-01

    To improve pharmacological characteristics of the delta-selective, cyclic peptide [D-Pen2, D-Pen5]enkephalin (DPDPE), modification by halogenation at the Phe4 residue was undertaken. The present study was to determine the extent [3H]DPDPE, [3H][p-Cl-Phe4]DPDPE and [p-125IPhe4]DPDPE crosses the blood-brain barrier, elicits analgesia and to characterize selective organ distribution and stability after i.v. administration. A significantly greater percentage of total [3H][p-Cl-Phe4]DPDPE reached the brain after 10, 20 and 40 min as compared to [3H]DPDPE and both peptides were significantly displaced by pretreatment with naloxone or naltrindole. The amount of [3H]DPDPE detected in the brain was greater than that of [p-125IPhe4]DPDPE. Distribution results revealed large amounts of the administered peptides were sequestered rapidly in the gall bladder and secreted into the small intestine. Hot-plate antinociception tests 5 min after i.v. administration (30 and 60 mg/kg) revealed [p-Cl-Phe4]DPDPE to elicit a much greater analgesic effect as compared to DPDPE or [p-125IPhe4]DPDPE. These results provide evidence that [p-Cl-Phe4]DPDPE has a greater apparent distribution to the brain and has a greater effect on the antinociception threshold as tested on the hot-plate than DPDPE or [p-125IPhe4]DPDPE. Stability of unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE was determined both in vitro and in vivo; both unlabeled and tritiated DPDPE and [p-Cl-Phe4]DPDPE remain intact. PMID:1762065

  3. Safety and Pharmacokinetics of Intravenous Zanamivir Treatment in Hospitalized Adults With Influenza: An Open-label, Multicenter, Single-Arm, Phase II Study

    PubMed Central

    Marty, Francisco M.; Man, Choy Y.; van der Horst, Charles; Francois, Bruno; Garot, Denis; Máňez, Rafael; Thamlikitkul, Visanu; Lorente, José A.; Álvarez-Lerma, Francisco; Brealey, David; Zhao, Henry H.; Weller, Steve; Yates, Phillip J.; Peppercorn, Amanda F.

    2014-01-01

    Background. Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza. Methods. Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed. Results. One hundred thirty patients received intravenous zanamivir (median, 5 days; range, 1–11) a median of 4.5 days (range, 1–7) after onset of influenza; 83% required intensive care. The most common influenza type/subtype was A/H1N1pdm09 (71%). AEs and serious AEs were reported in 85% and 34% of patients, respectively; serious AEs included bacterial pulmonary infections (8%), respiratory failure (7%), sepsis or septic shock (5%), and cardiogenic shock (5%). No drug-related trends in safety parameters were identified. Protocol-defined liver events were observed in 13% of patients. The 14- and 28-day all-cause mortality rates were 13% and 17%. No fatalities were considered zanamivir related. Pharmacokinetic data showed dose adjustments for renal impairment yielded similar zanamivir exposures. Ninety-three patients, positive at baseline for influenza by quantitative polymerase chain reaction, showed a median decrease in viral load of 1.42 log10 copies/mL after 2 days of treatment. Conclusions. Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir. Clinical Trials Registration NCT01014988. PMID:23983212

  4. Medroxyprogesterone acetate plasma levels after a single oral administration of two drug formulations.

    PubMed

    Pannuti, F; Strocchi, E; Longhi, A; Comparsi, R; Camaggi, C M

    1986-08-01

    A comparison has been made between the absorption of oral medroxyprogesterone acetate (MPA) in an aqueous suspension preparation and in syrup form. Plasma drug profiles were measured after a single administration of the two formulations in 17 advanced cancer patients. On average the standard form (aqueous suspension) gave peak levels which were lower than the syrup mixture. However, the wide intersubject spread in MPA plasma levels observed in both groups did not allow any statistical significance to be assigned to this difference. PMID:2945648

  5. Pharmacokinetics and pharmacodynamics following single and repeated nightly administrations of loprazolam, a new benzodiazepine hypnotic.

    PubMed Central

    McInnes, G T; Bunting, E A; Ings, R M; Robinson, J; Ankier, S I

    1985-01-01

    The pharmacokinetics of oral loprazolam and pharmacodynamic responses on the morning following nightly drug administration were examined after single and after seven consecutive 1 mg doses in six non-fasting healthy subjects. The serum concentration-time profiles for unchanged loprazolam measured by a specific high pressure liquid chromatography/gas chromatography (h.p.l.c./g.c.) method and for benzodiazepine material measured by radioimmunoassay (RIA) were qualitatively similar although RIA levels were consistently higher. Approximate elimination half-life of unchanged loprazolam after single doses was 8.0 h. For RIA measured material, approximate half-life was 11.7 h following acute administration and 12.8 h after seven consecutive doses. Compared to results after single doses, maximum serum concentration and AUC were greater following 1 week's treatment. Using RIA results, the increases were 27.2% (95% CL 6.9 to 47.4%) and 35.1% (95% CL 15.8 to 54.3%) respectively and using h.p.l.c./g.c. data, 11% (95% CL - 22.6% to 44.5%) and 41% (95% CL - 50.9 to 133.0%). After repeated doses of loprazolam, there were no significant changes with respect to results after single doses in psychomotor function assessed objectively by critical flicker fusion threshold or choice reaction time, or in sleep quality or behaviour on awakening assessed subjectively by 10 cm analogue scales. Mean time to maximum serum concentration was 4.95 h with considerable inter-individual variability (range 1-12 h) and there was a lag time of 1-1.5 h before drug was detectable in blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2860916

  6. Safety and Traceability in Patient Healthcare through the Integration of RFID Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration-Dispensation-Administration Circuit to Day Hospital Patients.

    PubMed

    Martínez Pérez, María; Vázquez González, Guillermo; Dafonte, Carlos

    2016-01-01

    This work presents the integration of the RFID technology with the aim of ensuring the traceability of patients and minimization of adverse events during the process of prescription-validation-elaboration-dispensation-administration of medication by means of the implementation of various passive and active WIFI RFID systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario Universitario A Coruña. Obtaining patient traceability and using the patient/drug binomial during this process allows us to minimize the occurrence of adverse events. The key points in this work are the unmistakably unique identification and accurate real time location of the controlled items (patients and medication). RFID technology has proved to be invaluable in assisting with the everyday clinical practice of a hospital, and has been successfully implemented in this environment and others. In services such as the day hospital, the implementation of said technology is further justified by the high costs of the service and the high risk to the patient. PMID:27483269

  7. The modulation of BDNF expression and signalling dissects the antidepressant from the reinforcing properties of ketamine: Effects of single infusion vs. chronic self-administration in rats.

    PubMed

    Caffino, Lucia; Di Chio, Marzia; Giannotti, Giuseppe; Venniro, Marco; Mutti, Anna; Padovani, Laura; Cheung, David; Fumagalli, Guido F; Yew, David T; Fumagalli, Fabio; Chiamulera, Cristiano

    2016-02-01

    Ketamine is a drug of abuse with a unique profile, which besides its inherent mechanism of action as a non-competitive antagonist of the NMDA glutamate receptor, displays both antidepressant and reinforcing properties. The major aim of our study was to find a molecular signature of ketamine that may help in discriminating between its reinforcing and antidepressant effects. To this end, we focused our attention on BDNF, a neurotrophin that has been shown to play a role in both antidepressant and reinforcing properties of several drugs. Rats were exposed to self-administer intravenous (IV) ketamine (S/A) for 43 days or to receive a single IV ketamine 0.5mg/kg, or vehicle infusion. Although the dose we employed is lower than that reported by the literature, it however yields Cmax values that correspond to those achieved in humans after antidepressant treatment. Our results show that while the single infusion of ketamine increased the neurotrophin expression in the hippocampus while reducing it in the ventral striatum, a feature shared with other antidepressants, the repeated self-administration reduced mBDNF expression and its downstream signalling in both ventral striatum and hippocampus. Further, we here show that phosphorylation of Akt is oppositely regulated by ketamine, pointing to this pathway as central to the different actions of the drug. Taken together, we here point to BDNF and its downstream signalling pathway as a finely tuned mechanism whose modulation might subserve the different features of ketamine. PMID:26706783

  8. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes

    PubMed Central

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  9. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes.

    PubMed

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  10. The Effect of Intravenous Administration of Active Recombinant Factor VII on Postoperative Bleeding in Cardiac Valve Reoperations; A Randomized Clinical Trial

    PubMed Central

    Payani, Narges; Foroughi, Mahnoosh; Dabbagh, Ali

    2015-01-01

    Background: Postoperative bleeding after cardiac reoperations is among the most complicating problems, both for the physicians and for the patients. Many modalities have been used to decrease its adverse effects and the need for blood products administration. Objectives: In a randomized double-blinded clinical trial of redo cardiac valve surgery in adult, the effect of active recombinant factor VII (rFVIIa) on postoperative bleeding was compared with placebo. Chest tube drainage was used for comparison of bleeding between the two groups. Patients and Methods: Two groups of 18 patients undergoing redo valve surgeries were treated and compared regarding chest tube drainage, need for blood products, prothrombin time (PT), partial thromboplastin time (PTT), hemoglobin and hematocrit, platelet count, and international normalized ratio (INR) in first 24 hours after surgery. Bleeding was assessed at 3rd, 12th, and 24th hour after operation. In rFVIIa group, 40 µg/kg of AryoSeven was administered before end of surgery and same volume of normal saline was administered as placebo in the control group. Results: Study groups showed no difference regarding baseline variables. Three patients in rFVIIa group (16.67%) and 13 in placebo group (72.23%) received blood products (P < 0.01). Chest tube blood drainage at 24th hour after operation was 315 ± 177 mL in rFVIIa group and 557 ± 168 mL in control group (P = 0.03). At third and 12th hour after operation, the difference was not statistically significant (P = 0.71 and P = 0.22, respectively). Postoperative ICU stay was not different; while extubation was longer in the placebo group (352 ± 57 vs. 287 ± 46 minutes; P = 0.003). Conclusions: Our study demonstrated the efficacy of rFVIIa in controlling postoperative bleeding in redo cardiac valve surgeries regarding subsequent blood loss and transfusion requirement; however, outcome results remains to be defined. PMID:25789239

  11. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

    PubMed

    Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

    2015-05-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

  12. Qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by liquid chromatography tandem mass spectrometry and its application after intravenous administration of felbinac trometamol injection.

    PubMed

    Zheng, Yunliang; Hu, Xingjiang; Liu, Jian; Wu, Guolan; Zhai, You; Wu, Lihua; Shentu, Jianzhong

    2015-04-01

    We present a method for the qualitative and quantitative analysis of felbinac and its major metabolites in human plasma and urine by HPLC-MS/MS and its application. Qualitative analysis through LC-Triple-TOF-MS/MS indicated that oxidization was the main phase-I metabolic pathway of felbinac in human, conjugation with sulfate and glucuronide groups produced at least 7 phase-II metabolites. Quantitative analysis through HPLC-MS/MS in MRM mode was developed and validated for the quantification of felbinac and its major metabolite (4'-hydroxyfelbinac) in human plasma and urine. Linear calibration curves were obtained for felbinac and 4'-hydroxyfelbinac in plasma and urine (r>0.996); intra- and inter-day precision values (RSD%) obtained were ranged from 1.13 to 6.49%, and the accuracy were between 95.9% and 108.6% for the two analytes. The pharmacokinetics and excretion analysis showed that the t1/2 of 4'-hydroxyfelbinac (8.25 ± 4.15 h) is a litter longer than that of felbinac (6.13 ± 2.01 h), but the mean AUC(0-t) value of felbinac was about 20 times higher than that of 4'-hydroxyfelbinac; excretion of felbinac and 4'-hydroxyfelbinac reached their peak values at about 3-6h after intravenous administration of felbinac trometamol in human. PMID:25706568

  13. Intravenous administration of the selective toll-like receptor 7 agonist DSR-29133 leads to anti-tumor efficacy in murine solid tumor models which can be potentiated by combination with fractionated radiotherapy

    PubMed Central

    Dovedi, Simon J.; Adlard, Amy L.; Ota, Yosuke; Murata, Masashi; Sugaru, Eiji; Koga-Yamakawa, Erina; Eguchi, Ken; Hirose, Yuko; Yamamoto, Setsuko; Umehara, Hiroki; Honeychurch, Jamie; Cheadle, Eleanor J.; Hughes, Gareth; Jewsbury, Philip J.

    2016-01-01

    Strategies to augment anti-cancer immune responses have recently demonstrated therapeutic utility. To date clinical success has been achieved through targeting co-inhibitory checkpoints such as CTLA-4, PD-1, and PD-L1. However, approaches that target co-activatory pathways are also being actively being developed. Here we report that the novel TLR7-selective agonist DSR-29133 is well tolerated in mice and leads to acute immune activation. Administration of DSR-29133 leads to the induction of IFNα/γ, IP-10, TNFα, IL-1Ra and IL-12p70, and to a reduction in tumor burden in syngeneic models of renal cancer (Renca), metastatic osteosarcoma (LM8) and colorectal cancer (CT26). Moreover, we show that the efficacy of DSR-29133 was significantly improved when administered in combination with low-dose fractionated radiotherapy (RT). Effective combination therapy required weekly administration of DSR-29133 commencing on day 1 of a fractionated RT treatment cycle, whereas no enhancement of radiation response was observed when DSR-29133 was administered at the end of the fractionated RT cycle. Combined therapy resulted in curative responses in a high proportion of mice bearing established CT26 tumors which was dependent on the activity of CD8+ T-cells but independent of CD4+ T-cells and NK/NKT cells. Moreover, long-term surviving mice originally treated with DSR-29133 and RT were protected by a tumor-specific memory immune response which could prevent tumor growth upon rechallenge. These results demonstrate that DSR-29133 is a potent selective TLR7 agonist that when administered intravenously can induce anti-tumor immune responses that can be further enhanced through combination with low-dose fractionated RT. PMID:26959743

  14. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist.

    PubMed

    Krieg, Arthur M; Efler, Susan M; Wittpoth, Michael; Al Adhami, Mohammed J; Davis, Heather L

    2004-01-01

    Subcutaneous injection of normal human volunteers with a B-class CpG oligodeoxynucleotide (ODN) TLR9 agonist, CPG 7909, induced a TH1-like pattern of systemic innate immune activation manifested by expression of IL-6, IL-12p40, IFN-alpha, and IFN-inducible chemokines. Serum IP-10 was found to be the most sensitive assay for subcutaneous CPG 7909 stimulation; its level was significantly increased in all subjects at all dose levels, including the lowest tested dose of just 0.0025 mg/kg. This pattern of chemokine and cytokine induction was markedly different from that previously reported to be induced by TLR9 stimulation in rodents, most likely reflecting species-specific differences in the cell types expressing TLR9. Subcutaneous CPG 7909 injection induced transient shifts in blood neutrophils, lymphocytes, and monocytes, consistent with the increased chemokine expression. Levels of acute phase reactants such as C-reactive protein were also increased. A second subcutaneous CPG 7909 injection administered 2 weeks after the first elicited similar immune responses, showing little or no tolerance to the effects of repeated in vivo TLR9 stimulation. Subjects developed dose-dependent transient injection site reactions and flu-like symptoms but otherwise tolerated injection well, with no evidence of organ toxicity or systemic autoimmunity. The activation of innate immunity was dependent on the route of ODN administration, since intravenous injection caused no such effects. These studies indicate that in vivo activation of TLR9 by subcutaneous administration of CPG 7909 could be a well-tolerated immunotherapeutic approach for induction of TH1 innate immune activation. PMID:15534490

  15. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    PubMed

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. PMID:21112749

  16. Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration.

    PubMed

    Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S

    2008-10-01

    The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning. PMID:19000263

  17. [Intravenous and subcutaneous immunoglobulin therapy].

    PubMed

    Thon, Vojtěch

    2013-07-01

    Patients with agammaglobulinaemia and hypogammaglobulinaemia require immunoglobulin G (IgG) replacement therapy to prevent serious infections. Since the 1950s, therapy with human immune globulin products has been the standard of treatment. Currently, the most common routes of administration of IgG replacement therapy are intravenous (IVIG) or subcutaneous (SCIG). The home therapy may improve the quality of life in patients who require lifelong IgG replacement. The -anti-IgA antibody test identifies the patients with the risk of anaphylactoid reactions in IVIG replacement. The SCIG delivery may be used in patients with anti-IgA antibodies and previous systemic reactions to IVIG. PMID:23964967

  18. Population pharmacokinetics of a single intramuscular administration of tulathromycin in adult desert tortoises (Gopherus agassizii).

    PubMed

    Kinney, M E; Lamberski, N; Wack, R; Foster, R; Neely, M; Tell, L; Gehring, R

    2014-10-01

    Tulathromycin, a long acting macrolide antibiotic, has demonstrated efficacy against respiratory pathogens including Mycoplasma bovis and M. hyopneumoniae. A pharmacokinetic study was performed to evaluate the clinical applicability of tulathromycin in desert tortoises following a single intramuscular dose of 5 mg/kg. A single blood sample was collected from 110 different desert tortoises at 0.25, 0.5, 1, 4, 8, 24, 48, 72, 120, and 240 h following drug administration. Plasma concentrations of the parent form of tulathromycin were measured using liquid chromatography/mass spectrometry. As each tortoise was only bled once, pharmacokinetic parameters were initially estimated using a naïve pooled data approach. Given the variability in the data, population-based compartmental modeling was also performed. Using nonparametric population compartmental modeling, a two-compartment model with first-order absorption and elimination best fit the data. An observed Cmax of 36.2 ± 29.7 μg/mL was detected at 0.25 h (observed Tmax ). The elimination half-life (T½el ) was long (77.1 h) resulting in detectable plasma concentrations 240 h postadministration. This study represents a preliminary step in evaluating the utility of tulathromycin in chelonian species and demonstrates that population data modeling offers advantages for estimating pharmacokinetic parameters where sparse data sampling occurs and there is substantial variability in the data. PMID:24611596

  19. Effect of Using Local Intrawound Vancomycin Powder in Addition to Intravenous Antibiotics in Posterior Lumbar Surgery: Midterm Result in a Single-Center Study

    PubMed Central

    Lee, Gun-Ill; Chun, Hyoung-Joon; Choi, Kyu-Sun

    2016-01-01

    Objective We conducted this study to report the efficacy of local application of vancomycin powder in the setting of surgical site infection (SSI) of posterior lumbar surgical procedures and to figure out risk factors of SSIs. Methods From February 2013 to December 2013, SSI rates following 275 posterior lumbar surgeries of which intrawound vancomycin powder was used in combination with intravenous antibiotics (Vanco group) were assessed. Compared with 296 posterior lumbar procedures with intravenous antibiotic only group from February 2012 to December 2012 (non-Vanco group), various infection rates were assessed. Univariate and multivariate analysis to figure out risk factors of infection among Vanco group were done. Results Statistically significant reduction of SSI in Vanco group (5.5%) from non-Vanco group (10.5%) was confirmed (p=0.028). Mean follow-up period was 8 months. Rate of acute staphylococcal SSIs reduced statistically significantly to 4% compared to 7.4% of non-Vanco group (p=0.041). Deep staphylococcal infection decreased to 2 compared to 8 and deep methicillin-resistant Staphylococcus aureus infection also decreased to 1 compared to 5 in non-Vanco group. No systemic complication was observed. Statistically significant risk factors associated with SSI were diabetes mellitus, history of cardiovascular disease, length of hospital stay, number of instrumented level and history of previous surgery. Conclusion In this series of 571 patients, intrawound vancomycin powder usage resulted in significant decrease in SSI rates in our posterior lumbar surgical procedures. Patients at high risk of infection are highly recommended as a candidate for this technique. PMID:27437012

  20. Kounis syndrome secondary to intravenous cephalosporin administration

    PubMed Central

    Venkateswararao, Sunkavalli; Rajendiran, Gopalan; Sundaram, Rathakrishnan Shanmuga; Mounika, Godavarthi

    2015-01-01

    Kounis syndrome is a clinical condition due to hypersensitivity that culminates into acute coronary syndrome (ACS) which can be fatal. A 36-year-old male with no conventional coronary risk factors presented elsewhere with a history of fever for 4 days, cough with expectoration, diarrhea and was treated with cephalosporin (Inj. Cefotaxime as an infusion) along with analgesics. He experienced generalized itching 5 minutes after cefotaxime infusion followed by sweating, headache, chest pain with facial and periorbital swelling for which he was rushed to our hospital. On examination he was afebrile with a low blood pressure. Electrocardiogram taken at an outside hospital revealed incomplete right bundle branch block and ST depression V3–V5. Investigations showed increase in troponin T. He was managed with anti-histamines and standard protocol for treatment of ACS. Coronary angiogram revealed normal coronaries. The patient improved symptomatically with treatment and was discharged on an anti-platelet, nitrate and a statin. PMID:26813799

  1. Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

    PubMed Central

    Huestis, M.A.; Cone, E.J.; Pirnay, S.O.; Umbricht, A.; Preston, K.L.

    2013-01-01

    Background Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. Methods Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography tandem mass spectrometry with limits of quantitation of 0.1 μg/L. Results Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3±1.0, 44.5±4.8, 85.2±7.7, 124.6±16.6, and 137.7±18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7±0.7 μg/L) after 16 mg IV administration. Conclusions Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg. PMID:23246635

  2. Ninety-day readmissions after degenerative cervical spine surgery: A single-center administrative database study

    PubMed Central

    Akamnonu, Chibuikem; Goldstein, Jeffrey A.; Errico, Thomas J.; Bendo, John A.

    2015-01-01

    Background Unplanned hospital readmissions result in significant clinical and financial burdens to patients and the healthcare system. Readmission rates and causes have been investigated using large administrative databases which have certain limitations in data reporting and coding. The objective of this study was to provide a description of 90 day post-discharge readmissions following surgery for common degenerative cervical spine pathologies at a large-volume tertiary hospital. The study also compared the readmission rates of patients who underwent anterior- and posterior-approach procedures. Methods The administrative records from a single-center, high-volume tertiary institution were queried using ICD-9 codes for common cervical pathology over a three year period to determine the rate and causes of readmissions within the 90 days following the index surgery. Results A total of 768 patients underwent degenerative cervical spine surgery during the three year study period. Within 90 days of discharge, 24 (3.13%) patients were readmitted; 16 (2.06%) readmissions were planned for lumbar surgery; 8 (1.04%) readmissions were unplanned. 640 patients underwent procedures involving an anterior approach and 128 patients underwent procedures involving a posterior approach. There were 14 (2.17%) planned readmissions in the anterior group and 2 (1.5%) in the posterior group. The unplanned readmission rate was 0.63% (4 patients) and 3.13% (4 patients) in the anterior and posterior groups, respectively. (p=0.0343). Conclusion The 90 day post-discharge unplanned readmission rate that followed elective degenerative cervical spine surgery was 1.04%. The unplanned readmission rate associated with posterior-approach procedures (3.13%) was significantly higher than that of anterior-approach procedures (0.63%). Level of evidence: IV PMID:26114088

  3. Simultaneous determination of parecoxib sodium and its active metabolite valdecoxib in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after intravenous and intramuscular administration.

    PubMed

    Liu, Meina; Yu, Qiuyang; Li, Ping; Zhu, Meng; Fang, Mingming; Sun, Bingjun; Sun, Mengchi; Sun, Yinghua; Zhang, Peng; He, Zhonggui; Sun, Jin; Wang, Yongjun; Liu, Xiaohong

    2016-06-01

    In this study, we developed and validated a new, rapid, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously determine parecoxib sodium (PX) and its active metabolite, valdecoxib (VX), in rat plasma. Plasma samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on a Kinetex C18 column (2.1mm×50mm, 2.6μm) with a gradient elution using methanol (A) and a 2mM ammonium acetate aqueous solution (B). The analysis was performed in less than 3min with a flow rate of 0.2mL/min. Ketoprofen was used as an internal standard (IS). Mass spectrometric detection was conducted with a triple quadrupole detector equipped with electrospray ionization in the negative ion mode (ESI(-)) using multiple reaction monitoring (MRM). The calibration curves were linear over the concentration ranges of 5-4000ng/mL for PX and 5-2000ng/mL for VX with all correlation coefficients greater than 0.998. The intra- and inter-day relative standard deviations (RSD) for both analytes were within 15% and the accuracy was within 85-115% at all quality control levels. The mean extraction recoveries for all analytes obtained from three concentrations of QC plasma samples were more than 89.0% efficient. Selectivity, matrix effect, dilution integrity and stability were also validated. The method was successfully used to investigate the pharmacokinetics of PX and VX in rat plasma after intravenous and intramuscular administration of PX. PMID:27107851

  4. Determination of cefdinir levels in rat plasma and urine by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics after oral and intravenous administration of cefdinir.

    PubMed

    Jin, Hyo-Eon; Kim, In-Bong; Kim, Chong-Kook; Maeng, Han-Joo

    2013-11-01

    A selective and sensitive liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar-RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10-10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra- and inter-day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration. PMID:23712418

  5. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  6. Similar Therapeutic Efficacy Between a Single Administration of Gene Therapy and Multiple Administrations of Recombinant Enzyme in a Mouse Model of Lysosomal Storage Disease

    PubMed Central

    Ferla, Rita; Claudiani, Pamela; Cotugno, Gabriella; Saccone, Paola; De Leonibus, Elvira

    2014-01-01

    Abstract Enzyme replacement therapy (ERT) has become the standard of care for several lysosomal storage disorders (LSDs). Despite ERT's undisputed efficacy, the requirement for multiple and costly administrations as well as ERT's limited improvement of some LSD manifestations prompts the search for better therapies. Using a mouse model of mucopolysaccharidosis VI, we compared the efficacy of a single intravascular administration of an adeno-associated viral vector targeting liver to weekly infusions of human recombinant enzyme at the same doses used in mucopolysaccharidosis VI patients. While gene therapy results in increased and stable levels of circulating enzyme up to 1 year after vector administration, ERT has typical peak-and-drop serum kinetics. Both therapies similarly reduced glycosaminoglycan levels in urine and tissues including heart valves and myocardium, with gene therapy improving skeletal skull abnormalities slightly better, although not significantly, than ERT. Both therapies seem to similarly improve animal motor performance, with gene therapy possibly associated with less animal distress. Thus, a single vector administration that converts liver into a factory organ for systemic secretion of therapeutic proteins is at least as effective as ERT in a mouse model of LSD, potentially eliminating problems with compliance and costs. Only testing in humans will prove whether this holds true in a clinical setting. PMID:24725025

  7. Similar therapeutic efficacy between a single administration of gene therapy and multiple administrations of recombinant enzyme in a mouse model of lysosomal storage disease.

    PubMed

    Ferla, Rita; Claudiani, Pamela; Cotugno, Gabriella; Saccone, Paola; De Leonibus, Elvira; Auricchio, Alberto

    2014-07-01

    Enzyme replacement therapy (ERT) has become the standard of care for several lysosomal storage disorders (LSDs). Despite ERT's undisputed efficacy, the requirement for multiple and costly administrations as well as ERT's limited improvement of some LSD manifestations prompts the search for better therapies. Using a mouse model of mucopolysaccharidosis VI, we compared the efficacy of a single intravascular administration of an adeno-associated viral vector targeting liver to weekly infusions of human recombinant enzyme at the same doses used in mucopolysaccharidosis VI patients. While gene therapy results in increased and stable levels of circulating enzyme up to 1 year after vector administration, ERT has typical peak-and-drop serum kinetics. Both therapies similarly reduced glycosaminoglycan levels in urine and tissues including heart valves and myocardium, with gene therapy improving skeletal skull abnormalities slightly better, although not significantly, than ERT. Both therapies seem to similarly improve animal motor performance, with gene therapy possibly associated with less animal distress. Thus, a single vector administration that converts liver into a factory organ for systemic secretion of therapeutic proteins is at least as effective as ERT in a mouse model of LSD, potentially eliminating problems with compliance and costs. Only testing in humans will prove whether this holds true in a clinical setting. PMID:24725025

  8. The acetylcholinesterase inhibitor rivastigmine does not alter total choices for methamphetamine, but may reduce positive subjective effects, in a laboratory model of intravenous self-administration in human volunteers.

    PubMed

    De La Garza, R; Mahoney, J J; Culbertson, C; Shoptaw, S; Newton, T F

    2008-04-01

    A human laboratory model of intravenous methamphetamine self-administration may facilitate study of putative treatments for methamphetamine addiction. We conducted a double-blind, placebo-controlled, between groups investigation of the acetylcholinesterase (AChE) inhibitor rivastigmine in non-treatment-seeking volunteers who met criteria for methamphetamine abuse or dependence. Safety and subjective effects data derived from days 1-10 of this protocol are described in a separate publication. In this report, we describe self-administration outcomes in participants randomized to treatment with rivastigmine (0 mg, N=7; 1.5 mg, N=6; 3 mg, N=9); data that were collected on days 11-15 of the inpatient protocol. On day 11, participants sampled two infusions of methamphetamine (0 and 30 mg, i.v.). On days 12-15, participants made ten choices each day to receive an infusion of either methamphetamine (3 mg, IV) or saline or a monetary alternative ($0.05-$16). The study design allowed for evaluation of differences in behavior on days in which infusions were performed by the physician (experimenter-administered) versus by the participant using a PCA pump (self-administered), and when monetary alternatives were presented in either ascending or descending sequence. The data show that rivastigmine (1.5 and 3 mg), as compared to placebo, did not significantly alter total choices for methamphetamine (p=0.150). Importantly, the number of infusion choices was greater when methamphetamine was available then when saline was available (p<0.0001), and the number of money choices was greater when saline was available then when methamphetamine was available (p<0.0001). The total number of choices for methamphetamine was not altered as a function of a participant's preferred route of methamphetamine use (p=0.57), and did not differ significantly whether they were experimenter-administered or self-administered (p=0.30). In addition, total choices for methamphetamine were similar made when

  9. Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats.

    PubMed

    Loram, Lisa C; Strand, Keith A; Taylor, Frederick R; Sloane, Evan; Van Dam, Anne-Marie; Rieger, Jayson; Maier, Steven F; Watkins, Linda R

    2015-05-01

    A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a single intrathecal administration of an A2AR agonist was able to attenuate motor symptoms induced by experimental autoimmune encephalopathy. Two A2AR agonists (CGS21680 and ATL313) significantly attenuated progression of motor symptoms following a single intrathecal administration at the onset of motor symptoms. OX-42, a marker of microglial activation, was significantly attenuated in the lumbar spinal cord following A2AR administration compared to vehicle. Therefore, A2AR agonists attenuate motor symptoms of EAE by acting on A2AR in the spinal cord. PMID:25653191

  10. Intravenous maternal -arginine administration to twin-bearing ewes, during late pregnancy, is associated with increased fetal muscle mTOR abundance and postnatal growth in twin female lambs.

    PubMed

    Sales, F; Sciascia, Q; van der Linden, D S; Wards, N J; Oliver, M H; McCoard, S A

    2016-06-01

    The aims of this study were to determine whether parenteral Arg administered to well-fed twin-bearing ewes from 100 to 140 d of pregnancy influences fetal skeletal muscle growth, the abundance and activation of mechanistic target of rapamycin (mTOR) protein, and postnatal muscle growth of the offspring. Ewes fed 100% of NRC-recommended nutrient requirements for twin-bearing ewes were administered an intravenous bolus of either 345 μmol Arg HCl/kg BW or saline solution (Control) 3 times per day. At 140 d of pregnancy (P140), a group of 11 Control and 9 Arg-treated ewes were euthanized and hind leg muscles and longissimus dorsi (LD) were excised and weighed. A sample of LD was snap frozen in liquid nitrogen for later analysis of free AA (FAA) concentration, mTOR abundance and phosphorylation, and biochemical indices (DNA, RNA, and protein content). For the remaining 25 ewes (Arg, = 13, and Control, = 12), Arg administration was continued until the initiation of parturition and ewes were allowed to lamb. Lambs were weaned at postnatal Day 82 and grazed on pasture until postnatal day 153 (PN153), when a subset of 20 lambs ( = 10 per group) was euthanized. At P140, only the psoas major was heavier in the Arg-administered group compared with the Control group. Female lambs from ewes supplemented with Arg (Arg-F) had increased abundance of total mTOR, RNA concentration, and RNA:DNA ratio in LD compared with female lambs from Control ewes (Con-F), whereas males did not differ. At PN153, Arg-F were heavier than Con-F and had heavier LD and plantaris and a trend for heavier psoas major muscles compared with Con-F. In contrast, BW and individual muscle weights did not differ in male lambs. Lambs from Arg-treated ewes had heavier semimembranosus and tended to have heavier biceps femoris compared with Control lambs. The RNA concentration in LD was greater in Arg-F compared with Con-F, and DNA concentration was greater in the Arg group compared with the Control group. In

  11. Pharmacokinetic profiles of meloxicam in turtles (Trachemys scripta scripta) after single oral, intracoelomic and intramuscular administrations.

    PubMed

    Di Salvo, A; Giorgi, M; Catanzaro, A; Deli, G; della Rocca, G

    2016-02-01

    Meloxicam is an anti-inflammatory and analgesic drug used to treat many pathological conditions in turtles. With the aim to fill the lack of data about its pharmacokinetic in this species, eighteen turtles (Trachemys scripta scripta) were divided in three groups and treated with a single dose of meloxicam (0.2 mg/kg) by intramuscular, intracoelomic and oral route, respectively. At scheduled time points, blood samples were collected and meloxicam concentrations were determined by HPLC. Pharmacokinetic parameters were calculated from the obtained concentration-time curves. After intramuscular treatment, a plasma peak of meloxicam equal to 1590.03 ± 1845.32 ng/mL (mean ± SD) and a Tmax of 1.17 ± 0.45 h were reached, indicating a quick absorption of the drug. The intracoelomic administration brought to the largest AUC (12621.04 ± 6203.79 h*ng/mL) and to a Cmax and a Tmax equal to 1154.52 ± 662.78 ng/mL and 2.82 ± 1.39 h, respectively. Following oral treatment, the plasma concentrations of meloxicam were very low indicating a scarce absorption. Further studies are warranted to determine the effective plasma concentration of meloxicam in turtles and, consequently, the dosage regimen. PMID:26789011

  12. Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

    PubMed

    Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

    2016-01-01

    Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. PMID:26726988

  13. Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration.

    PubMed

    Pang, Chengfang; Brunelli, Andrea; Zhu, Conghui; Hristozov, Danail; Liu, Ying; Semenzin, Elena; Wang, Wenwen; Tao, Wuqun; Liang, Jingnan; Marcomini, Antonio; Chen, Chunying; Zhao, Bin

    2016-03-01

    With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs (ζ potential = +46.5 mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs (ζ potential = -16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications. PMID:25962681

  14. 78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Clinical Trial Design for Intravenous Fat Emulsion Products... ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support registration of intravenous fat...

  15. Intravenous smart pumps.

    PubMed

    Harding, Andrew D

    2013-01-01

    Intravenous (IV) smart pumps provide substantial safety features during infusion. However, nurses need to understand the requisite education necessary to fully benefit from and improve IV smart pump use and clinical integration. Failure to use IV smart pumps places the nurse and patient at increased risk. PMID:23558918

  16. Intravenous radionuclide cystography for the detection of vesicorenal reflux

    SciTech Connect

    Pollet, J.E.; Sharp, P.F.; Smith, F.W.; Davidson, A.I.; Miller, S.S.

    1981-01-01

    Intravenous radionuclide cystography using a single intravenous injection of 99mtechnetium diethylenetriaminepentaacetic acid, provides information on individual kidney function, coarse anatomy and vesicorenal reflux. This study investigates the effectiveness of intravenous radionuclide cystography in detecting reflux. In 58 children intravenous radionuclide cystography detected 53 ureters with reflux compared to 32 detected by voiding cystography. This difference was investigated further with patients in whom other test suggested reflux. While there was no statistically significant difference for patients having pyelonephritis or hydronephrosis, intravenous radionuclide cystography detected significantly more ureters with reflux in patients with abnormal ureteral orifices or infected urine and, therefore, predisposed to reflux. Intravenous radionuclide cystography is a more comprehensive and sensitive test for vesicorenal reflux than voiding cystography.

  17. [Segmental testicular infarction. Unusual complication of intravenous immunoglobulin therapy for multifocal motor neuropathy].

    PubMed

    Rüb, J; Rehmann, R; von Landenberg, N; Roghmann, F; Stude, P; Tegenthoff, M; Noldus, J; Pastor, J

    2015-10-01

    We describe the previously unknown case of segmental testicular infarction as an iatrogenic complication of intravenous immunoglobulin administration in a patient with multifocal motor neuropathy. PMID:26303740

  18. Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses

    SciTech Connect

    Kopp, Eva Katharina; Dekant, Wolfgang

    2009-03-01

    The rodent carcinogen acrylamide (AA) is formed during preparation of starch-containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide (GA). After metabolic processing, the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), rac-N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) and rac-N-acetyl-S-(1-carbamoyl-moyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA-sulfoxide. The aim of this study was to assess potential species-differences in AA-toxicokinetics in rats and humans after single oral administration of doses similar to the daily human dietary exposure. Male Fischer 344 rats (n = 5/dose group) were administered 20 and 100 {mu}g/kg b.w. {sup 13}C{sub 3}-AA in deionized water via oral gavage. Human subjects (n = 3/gender) were orally administered 0.5 and 20 {mu}g/kg b.w. {sup 13}C{sub 3}-AA with drinking water. Urine samples were collected in intervals for 96 and 94 h, respectively. Urinary concentrations of {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide were monitored by liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3% and 70.5% of the 20 and 100 {mu}g/kg b.w. doses in rats and for 71.3% and 70.0% of the 0.5 and 20 {mu}g/kg b.w. doses in humans. In rats, {sup 13}C{sub 3}-AAMA accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered as {sup 13}C{sub 3}-GAMA; {sup 13}C{sub 3}-AAMA-sulfoxide was not detected in rat urine. In humans, {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide accounted for 51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose, respectively. The obtained results suggest that the extent of AA bioactivation to GA in humans is lower than in rodents.

  19. Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

    PubMed

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick

    2010-06-01

    To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety. PMID:20806657

  20. Efficacy of Intravenous Paracetamol Versus Intravenous Morphine in Acute Limb Trauma

    PubMed Central

    Jalili, Mohammad; Mozaffarpour Noori, Ali; Sedaghat, Mojtaba; Safaie, Arash

    2016-01-01

    Background: Efficient pain management is one of the most important components of care in the field of emergency medicine. Objectives: This study was conducted to compare intravenous paracetamol and intravenous morphine sulfate for acute pain reduction in patients with limb trauma. Patients and Methods: In a randomized double-blinded clinical trial, all patients (aged 18 years and older) with acute limb trauma and a pain score of greater than 3/10 in the emergency department were recruited; they received either 1 g intravenous paracetamol or 0.1 mg/kg intravenous morphine sulfate over 15 minutes. The primary outcome was the pain score measured on a numerical rating scale at 0, 15 and 30 minutes after commencing drug administration. The requirement for rescue analgesia and the frequency of adverse reactions were also recorded. Results: Sixty patients randomly received either IV paracetamol (n = 30) or IV morphine (n = 30). The mean reduction in numerical rating scale pain intensity scores at 30 minutes was 3.86 (± 1.61) for paracetamol, and 2.16 (± 1.39) for morphine. However, pain relief was significantly higher in the paracetamol group compared to the morphine group (P < 0.001). Four patients in the paracetamol group and 15 patients in the morphine group needed rescue analgesia and the difference was significant (P = 0.05). Conclusions: Intravenous paracetamol appears to provide better analgesia than intravenous morphine in acute limb trauma. Further larger studies are required. PMID:27218042

  1. Multiple Intravenous Infusions Phase 1b

    PubMed Central

    Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

    2012-01-01

    Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all

  2. The effects of intravenous ciprofloxacin on the electrocardiogram of healthy dogs.

    PubMed

    Ghaffari, Masoud Selk; Parsamehr, Reza

    2009-12-01

    The purpose of this study was to evaluate the electrocardiographic effects of single intravenous dose of ciprofloxacin in dogs. Ten adult cross-breed dogs of both sexes were selected as the sample population. Baseline electrocardiographic values were recorded just before drug administration. Then the dogs received intravenous infusion of ciprofloxacin (10 mg/kg) over the fifteen minutes. The ECGs recorded at 15, 30, 60 and 120 minutes after ciprofloxacin administration. The ECG measurements of heart rate, PR interval, QRS interval, ST segment, T-wave amplitude and QT interval were taken from lead II. There was a small but significant increase in the longest QT intervals over baseline at T₆₀ (P = 0.041). The mean PR intervals, QTc intervals, JT intervals, ST segment, T-wave amplitude did not differ significantly before and after ciprofloxacin except for JT intervals at T₆₀ (P = 0.041). At this measurement point, there was an increased QT interval value of 0.02 second or 9.51% in comparison to the baseline. In Conclusions, Only minor QT intervals changes were observed after ciprofloxacin injection. Despite the occurrence of ECG changes following intravenous ciprofloxacin administration neither dangerous rhythm disturbances nor serious ECG changes were seen in this study. PMID:19728129

  3. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    PubMed

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms. PMID:2686417

  4. Single-dose intravenous paracetamol or propacetamol for prevention or treatment of postoperative pain: a systematic review and meta-analysis.

    PubMed

    McNicol, E D; Tzortzopoulou, A; Cepeda, M S; Francia, M B D; Farhat, T; Schumann, R

    2011-06-01

    Paracetamol is the most commonly prescribed analgesic for the treatment of acute pain. The efficacy and safety of i.v. formulations of paracetamol is unclear. We performed a systematic search (multiple databases, bibliographies, any language, to May 2010) for single-dose, randomized, controlled clinical trials of propacetamol or i.v. paracetamol for acute postoperative pain in adults or children. Thirty-six studies involving 3896 patients were included. For the primary outcome, 37% of patients (240/367) receiving propacetamol or i.v. paracetamol experienced at least 50% pain relief over 4 h compared with 16% (68/527) receiving placebo (number needed to treat=4.0; 95% confidence interval, 3.5-4.8). The proportion of patients in propacetamol or i.v. paracetamol groups experiencing at least 50% pain relief diminished over 6 h. Patients receiving propacetamol or paracetamol required 30% less opioid over 4 h and 16% less opioid over 6 h than those receiving placebo. However, this did not translate to a reduction in opioid-induced adverse events (AEs). Similar comparisons between propacetamol or i.v. paracetamol and active comparators were either not statistically significant, not clinically significant, or both. AEs occurred at similar rates with propacetamol or i.v. paracetamol and placebo. However, pain on infusion occurred more frequently in those receiving propacetamol compared with placebo (23% vs 1%). A single dose of either propacetamol or i.v. paracetamol provides around 4 h of effective analgesia for about 37% of patients with acute postoperative pain. Both formulations are associated with few AEs, although patients receiving propacetamol have a higher incidence of pain on infusion. PMID:21558067

  5. Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration.

    PubMed

    Upmeier, A; Degen, G H; Diel, P; Michna, H; Bolt, H M

    2000-10-01

    Bisphenol A [BPA; 2,2-bis-(4-hydroxyphenyl)-propane] is a monomer used in the manufacture of resins with a wide range of applications, e.g. plastic coatings in the food packaging industry. BPA has been shown to have a weak oestrogenic activity in vitro and in vivo. Despite its low oestrogenic potency there is concern that, as a consequence of slow clearance, BPA might reach biologically significant levels in humans and animals exposed to environmental levels. To address this concern, we assessed the kinetic behaviour of BPA in female DA/Han rats. Groups of female rats received 10 mg BPA/kg body weight intravenously or 10 or 100 mg BPA/kg body weight orally (by gavage). Blood samples were collected at different time-points and plasma was prepared. Free BPA in the samples was isolated by fluid-fluid extraction. BPA was measured by GC-MS which allowed the reliable determination of BPA concentrations as low as approximately 10 ng/ml plasma. Immediately after i.v. administration, the BPA plasma concentration was in the range of about 15 microg/ml and decreased rapidly within the first hour (to 700 ng/ml). The levels declined further (100 ng/ml at 2 h), and after 24 h the analytical detection limit was reached. BPA was detected in plasma as early as 10 min after gavage administration, indicating rapid initial uptake from the gastrointestinal tract. Absorption of BPA was variable. In animals receiving 10 mg/kg, maximal plasma levels were reached after 1.5 h (31 ng/ ml) and 6 h (40 ng/ml). In animals receiving 100 mg/kg, plasma levels reached maxima around 30 min (150 ng/ml) and 3 h (134 ng/ml) after administration. After 48 h BPA was at or below the detection limit in both dose groups. Fluctuations in the BPA plasma concentrations over time point to the possibility of enterohepatic recirculation and protracted absorption from the gastrointestinal tract. Using the area under the concentration-time curves (AUCs), low bioavailabilities of 16.4% and 5.6% were calculated for

  6. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... Administration (FDA) is correcting a notice that appeared in the Federal Register of July 6, 2012 (77 FR 40069... Spring, MD 20993-0002, 301- 796-3485, astrid.lopezgoldberg@fda.hhs.gov . SUPPLEMENTARY INFORMATION: In FR... are labeled for human use, and persons who manufacture or cause the manufacture or distribution...

  7. Reduced administration of rasburicase for tumor lysis syndrome: A single-institution experience

    PubMed Central

    TAKAI, MIHOKO; YAMAUCHI, TAKAHIRO; MATSUDA, YASUFUMI; TAI, KATSUNORI; IKEGAYA, SATOSHI; KISHI, SHINJI; URASAKI, YOSHIMASA; YOSHIDA, AKIRA; IWASAKI, HIROMICHI; UEDA, TAKANORI

    2015-01-01

    In the present study, the dosage and duration of rasburicase administration were retrospectively evaluated for the ability to control the serum uric acid (S-UA) level in 13 patients diagnosed with hematological malignancies and tumor lysis syndrome (TLS), or those at risk of developing TLS, at the University of Fukui Hospital. At the time of diagnosis, seven patients already exhibited laboratory TLS, and three demonstrated clinical TLS. All patients received rasburicase in addition to chemotherapy agents. The median dose was 0.19 mg/kg (range, 0.13–0.25 mg/kg), and the median duration was four days (range, 1–7 days). Six patients sequentially received a xanthine oxidase inhibitor, allopurinol or febuxostat. The primary estimate was the normalization of the S-UA level at the end of rasburicase treatment and on treatment day seven. The average S-UA level prior to treatment was 10.4±4.5 mg/dl (mean ±standard deviation), and 11 out of 13 patients demonstrated a S-UA level >7 mg/dl. The S-UA level at the end of rasburicase administration was 0.5±1.5 mg/dl and the S-UA level at day seven was 1.4±1.5 mg/dl. All the patients achieved normalization of the S-UA level. On day seven subsequent to the initiation of treatment, the patients receiving rasburicase for a maximum of three days exhibited an S-UA level of 1.9±1.8 mg/dl, while the patients receiving rasburicase for longer than three days demonstrated an S-UA level of 1.0±1.3 mg/dl (P=0.20; Mann-Whitney test). The administration of 0.13 mg/kg and 0.22 mg/kg resulted in comparable UA level reductions. The administration of allopurinol or febuxostat following rasburicase administration suppressed the re-increase in S-UA level. Therefore, it was concluded that reduced administration of rasburicase successfully controlled the S-UA level in TLS. PMID:26137024

  8. Toxico-kinetics, recovery, and metabolism of napropamide in goats following a single high-dose oral administration.

    PubMed

    Pahari, A K; Majumdar, S; Mandal, T K; Chakraborty, A K; Bhattacharyya, A; Chowdhury, A

    2001-04-01

    Toxicokinetic behavior, recovery and metabolism of napropamide (a pre-emergent herbicide) and its effect on Cytochrome P(450) of liver microsomal pellet were studied following a single high-dose oral administration of 2.5 g kg(-1) and continuous (7 days) oral administration of 500 mg kg(-1) in black Bengal goat. Napropamide was detected in blood at 15 min and the maximum quantity was recovered at 3 h after administration. The absorption rate constant (Ka) value was low indicating poor absorption from the gastrointestinal tract. High elimination half-life (t(1/2) beta) and low body clearance (Cl(B)) values coupled with higher transfer of compound from tissue to central compartment (K(21)) suggest that napropamide persisted in the blood for a long time, i.e., after 72 h of oral administration. The recovery percentage of napropamide, including metabolites, from goats varied from 75.94 to 80.08 and excretion of the parent compound through feces varied from 18.86 to 21.59%, indicating that a major portion of the orally administered napropamide was absorbed from the gastrointestinal tract of goat. Napropamide significantly increased the Cytochrome P(450) content of liver microsomal pellet. The recovery of metabolites from feces, urine, and tissues ranged from 4.2--6.2, 40.81--49.42, and 2.7--11.6%, respectively, during a 4--7 day period. The material balance of napropamide (including metabolites) following a single high-dose oral administration at 2.5 g kg(-1) during 4--7 days after dosing was found to be in the range of 75--80%. PMID:11308331

  9. Enhanced Absorption of Nasulin™, an Ultrarapid-Acting Intranasal Insulin Formulation, Using Single Nostril Administration in Normal Subjects

    PubMed Central

    Stote, Robert; Miller, Michael; Marbury, Thomas; Shi, Leon; Strange, Poul

    2011-01-01

    Background This pharmacokinetic (PK) study was designed to investigate the maximum intranasal insulin dose that could be achieved by repeated doses in a single nostril of a nasal spray of recombinant regular human insulin 1% in combination with cyclopentadecalactone (CPE-215) 2%, a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals, Inc.). Method A nine-period crossover study of 8 healthy, nonsmoking subjects (ages 18–50, body mass index <33 kg/m2, weight >70 kg) were studied. In a fasted state, subjects were randomly given 25, 50, and 75 U in a single nostril on the first day and randomly given 50, 75, and 100 U doses utilizing both nostrils on two subsequent days. After a 45-minute PK assessment, subjects were given a meal. To determine the mechanism of enhanced absorption in a single nostril, a second study utilizing 24 subjects under similar conditions received 25 U, placebo (P) that included CPE-215 plus 25 U, and 50 U in a single nostril. Results Single nostril administration revealed enhanced absorption with maximum concentrations (Cmax) of 13, 65, and 96 µU/ml for the 25, 50, and 75 U doses, respectively. Dual nostril administration in two cohorts resulted in Cmax of 31/42, 65/52, and 88/79 µU/ml for the 50, 75, and 100 U, respectively. In the second cohort, Cmax was 23, 19, 56 µU/ml for the 25, P + 25, and 50 U doses, respectively. Conclusions Repeated dosing in a single nostril resulted in enhanced absorption; this was not due to the increased CPE-215 but to the increased insulin administered. PMID:21303633

  10. The absorption and metabolism of a single L-menthol oral versus skin administration: Effects on thermogenesis and metabolic rate.

    PubMed

    Valente, Angelica; Carrillo, Andres E; Tzatzarakis, Manolis N; Vakonaki, Elena; Tsatsakis, Aristidis M; Kenny, Glen P; Koutedakis, Yiannis; Jamurtas, Athanasios Z; Flouris, Andreas D

    2015-12-01

    We investigated the absorption and metabolism pharmacokinetics of a single L-menthol oral versus skin administration and the effects on human thermogenesis and metabolic rate. Twenty healthy adults were randomly distributed into oral (capsule) and skin (gel) groups and treated with 10 mg kg(-1) L-menthol (ORALMENT; SKINMENT) or control (lactose capsule: ORALCON; water application: SKINCON) in a random order on two different days. Levels of serum L-menthol increased similarly in ORALMENT and SKINMENT (p > 0.05). L-menthol glucuronidation was greater in ORALMENT than SKINMENT (p < 0.05). Cutaneous vasoconstriction, rectal temperature and body heat storage showed greater increase following SKINMENT compared to ORALMENT and control conditions (p < 0.05). Metabolic rate increased from baseline by 18% in SKINMENT and 10% in ORALMENT and respiratory exchange ratio decreased more in ORALMENT (5.4%) than SKINMENT (4.8%) compared to control conditions (p < 0.05). Levels of plasma adiponectin and leptin as well as heart rate variability were similar to control following either treatment (p > 0.05). Participants reported no cold, shivering, discomfort, stress or skin irritation. We conclude that a single L-menthol skin administration increased thermogenesis and metabolic rate in humans. These effects are minor following L-menthol oral administration probably due to faster glucuronidation and greater blood menthol glucuronide levels. PMID:26429629

  11. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics.

    PubMed

    Okuno, G; Kawakami, F; Tako, H; Kashihara, T; Shibamoto, S; Yamazaki, T; Yamamoto, K; Saeki, M

    1986-04-01

    A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus. PMID:3522147

  12. Mast cell accumulation precedes tissue fibrosis induced by intravenously administered amorphous silica nanoparticles.

    PubMed

    Zhuravskii, Serge; Yukina, Galina; Kulikova, Olga; Panevin, Alexey; Tomson, Vladimir; Korolev, Dmitry; Galagudza, Michael

    2016-05-01

    Despite the increasing use of amorphous silica nanoparticles (SNPs) in biomedical applications, their toxicity after intravenous administration remains a major concern. We investigated the effects of single 7 mg/kg intravenous infusions of 13 nm SNPs on hemodynamic parameters in rats. Hematological and biochemical parameters were assessed at 7, 30, and 60 d post treatment. Silicon content in the liver, lungs, heart, and kidney was analyzed, as well as tissue histology with special emphasis on mast cell (MC) content. SNP infusion had no effect on hemodynamics, nor did it alter hematological or biochemical parameters. SNP retention in the liver was conspicuous for up to 60 d. Among the other organs analyzed, silicon content was significantly increased only in the lung at 1-h post infusion. Despite the relatively low dose, SNP administration caused extensive liver remodeling, including the formation of multiple foreign body-type granulomas starting 7 d post treatment, and subsequent development of fibrosis. Histopathological changes in the liver were not preceded by hepatocyte necrosis. We found increased MC abundance in the liver, lungs, and heart starting on day 30 post treatment. MC recruitment in the liver preceded fibrosis, suggesting that MCs are involved in liver tissue remodeling elicited by intravenously administered SNPs. PMID:27055490

  13. Residual effects and skills related to driving after a single oral administration of diazepam, medazepam or lorazepam.

    PubMed Central

    Seppälä, K; Korttila, K; Häkkinen, S; Linnoila, M

    1976-01-01

    Psychomotor skills and visual functions related to driving were measured double-blind cross-over in ten healthy volunteers before, and 1,3,5 and 7 h after a single oral administration of diazepam (10mg), medazepam (15 mg) or lorazepam (2.5 mg). The late effects of lorazepam were tested in seven other subjects 12 and 24 h after the administration. Lorazepam impaired almost all the measured skills more (P less than 0.05 to 0.001) than diazepam, medizepam or the placebo. The lorazepam impairment of reactive skills and flicker fusion discrimination remained statistically significant (P less than 0.05) for as long as 12 h. Medazepam impaired only reactive skills and flicker fusion, the latter remaining impaired (P less than 0.05) for as long a 5 h after the administration. The magnitude and duration of the effects of diazepam were intermediate between those of lorazepam and medazepam. Diazepam impaired perceptual speed and reactive and co-ordinative skills as well as flicker fusion discrimination and visual parameters related to driving. Slight impairments in performance were measurable for up to 5 h after administration but at 7 h the results resembled those measured after the placebo. The lack of alterations in adaptation to darkness, sensitivity to brightness or visual discrimination ability in bright counterlight at a time when flicker fusion discrimination was severely depressed suggests that an impaired ability to discriminate flickering light is of no or little clinical significance to driving ability. It is concluded that patients receiving a 2.5 mg dose of lorazepam should not drive or operate machinery for 24 h after the administration. After diazepam (10 mg) or medazepam (15 mg) patients should refrain from driving or participating inskilled performances for only 5 to 7 hours. PMID:9967

  14. Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.

    PubMed

    Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

    2004-01-01

    A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. PMID:14597158

  15. Reduced intravenous toxicity of amiodarone nanosuspension in mice and rats.

    PubMed

    Barle, Ester Lovšin; Cerne, Manica; Peternel, Luka; Homar, Miha

    2013-07-01

    The toxicity of amiodarone Lek formulation (test formulation) was investigated after a single intravenous (i.v.) administration to mice and rats. When compared to the reference item, Cordarone (Cordarone(®); Wyeth Pharmaceuticals Inc., Collegeville, Pennsylvania, USA), median lethal dose (LD(50)) after i.v. administration in female mice was 294.0 mg/kg body weight (b.w.) for the test formulation and 227.5 mg/kg b.w. for Cordarone. In female rats after i.v. administration, the LD(50) value was 269.9 mg/kg b.w. for the test formulation and 192.4 mg/kg b.w. for Cordarone. By altering the particle size of amiodarone in the Lek formulation, we were able to improve the solubility of amiodarone, thereby decreasing the number and quantity of excipients needed for preparation of the i.v. formulation and, consequently, reduced the acute toxic effects observed in the present study. PMID:22950665

  16. Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

    PubMed

    Leary, A; Barthe, L; Clavel, T; Sanchez, C; Oulmi-Castel, M; Paillard, B; Edmond, J M; Brunner, V

    2016-01-01

    Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration. PMID:25989284

  17. Comparing the Efficacy of Intravenous Acetaminophen and Intravenous Meperidine in Pain Relief After Outpatient Urological Surgery

    PubMed Central

    Kolahdouzan, Khosro; Eydi, Mahmood; Mohammadipour Anvari, Hassan; Golzari, Samad EJ; Abri, Reyhaneh; Ghojazadeh, Morteza; Ojaghihaghighi, Seyed Hossein

    2014-01-01

    Background: Pain relief after surgery is an essential component of postoperative care. Objectives: The purpose of this study was to compare the efficacy of intravenous acetaminophen and intravenous meperidine in pain relief after outpatient urological surgery. Patients and Methods: In a prospective, randomized, double-blind clinical trial, 100 outpatients of urological surgery were studied in two groups of acetaminophen (A) and meperidine (M). Patients in group A received 1g of acetaminophen in 100 mL saline within 15 minutes and patients in group M received a single intravenous injection of meperidine 0.5 mg/kg, 15 minutes prior to the end of operation. Postoperative pain was recorded using visual analog scale (VAS). Vital signs, nausea, vomiting, dizziness and respiratory depressions were compared between the two groups. Results: Pain severity in patients treated with intravenous acetaminophen six hours after the operation within one-hour interval was significantly lower than meperidine group (P < 0.0001). Ninety patients in the meperidine group and five patients in the acetaminophen group required additional doses of analgesics. Nausea was significantly lower in acetaminophen group than meperidine group. Conclusions: Intravenous acetaminophen reduced pain following outpatient urological surgery more significantly than meperidine. PMID:25798377

  18. Investigation of Japanese quail (Coturnix japonica) as a pharmacokinetic model for cockatiels (Nymphicus hollandicus) and Poicephalus parrots via comparison of the pharmacokinetics of a single intravenous injection of oxytetracycline hydrochloride.

    PubMed

    Osofsky, A; Tell, L A; Kass, P H; Wetzlich, S E; Nugent-Deal, J; Craigmill, A L

    2005-12-01

    The purpose of this study was to determine whether Japanese quail (Coturnix japonica) would serve as a pharmacokinetic animal model for two small companion parrots: cockatiels (Nymphicus hollandicus) and Poicephalus parrots. Oxytetracycline (OTC) was the pharmacologic agent chosen for this study as it is eliminated primarily by renal glomerular filtration and undergoes minimal metabolism. A single intravenous injection of 20 mg/kg oxytetracycline hydrochloride was administered to the three study groups and blood samples were obtained at 5, 10, 15, and 30 min post-OTC injection as well as 1, 2, 4, 8, 12 and 24 h post-OTC injection. Quantification of plasma OTC was accomplished using a standardized microbial inhibition assay. Naïve-pooled data (NPD) analysis of the plasma concentration-time profile of OTC best fit a two-compartment open model for all three avian species. Noncompartmental analysis of the mean data yielded the following parameters for quail, cockatiels and Poicephalus parrots respectively: lambda(z) = 3.14, 4.57, 3.71 h; AUC = 38.9, 42.7, 49.6 microg x h/mL; and Cl = 514, 468, 403 mL/h/kg. Based on the similarity of these pharmacokinetic parameters, it appears that quail could be used as a model species to predict the appropriate OTC dosing regimen for small psittacine birds. A bootstrap procedure was also applied to these sparse data sets for both compartmental and noncompartmental analysis. The bootstrap procedure allowed for the calculation of variability of parameters; however, the estimates of the parameters were very similar to those calculated using the NPD and the data mean values. PMID:16343282

  19. Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise.

    PubMed

    Nakhostin-Roohi, Babak; Niknam, Zahra; Vaezi, Nasrin; Mohammadi, Sadollah; Bohlooli, Shahab

    2013-01-01

    Methylsulfonylmethane (MSM) is a sulfur-containing compound commonly found in diet and known to reduce oxidative stress. This trial was conducted to determine whether single dose supplementation with MSM attenuates post-exercise oxidative stress in healthy untrained young men. Sixteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into 2 groups: Methylsulfonylmethane (MSM) (n = 8) and placebo (n = 8). The participants took supplementation or placebo before running on treadmill for 45 min at 75% VO2max. The MSM supplementation was prepared in water as 100 mg/ kg body weight. The placebo group received water. Serum Malondealdehyde (MDA), uric acid, bilirubin, protein carbonyl (PC) and plasma vitamin E levels were determined as the markers of oxidative stress. Plasma GSH (reduced Glutathione) and total antioxidant capacity (TAC) were measured as markers of plasma antioxidant system. MSM supplementation successfully lowered serum PC 2 and 24 h after exercise. Plasma TAC in MSM group was higher at 24 h after exercise. Serum level of uric acid and bilirubin were significantly low immediately after exercise in MSM supplemented group. There was no significant difference between groups in terms of plasma GSH level. These results complement earlier studies showing anti-oxidant effect of MSM and suggest that single dose oral supplementation with MSM lowers exercise induced oxidative stress in healthy untrained young men, but is not adequate to significantly affect plasma GSH level. PMID:24523764

  20. Intravenous Fluid Generation System

    NASA Technical Reports Server (NTRS)

    McQuillen, John; McKay, Terri; Brown, Daniel; Zoldak, John

    2013-01-01

    The ability to stabilize and treat patients on exploration missions will depend on access to needed consumables. Intravenous (IV) fluids have been identified as required consumables. A review of the Space Medicine Exploration Medical Condition List (SMEMCL) lists over 400 medical conditions that could present and require treatment during ISS missions. The Intravenous Fluid Generation System (IVGEN) technology provides the scalable capability to generate IV fluids from indigenous water supplies. It meets USP (U.S. Pharmacopeia) standards. This capability was performed using potable water from the ISS; water from more extreme environments would need preconditioning. The key advantage is the ability to filter mass and volume, providing the equivalent amount of IV fluid: this is critical for remote operations or resource- poor environments. The IVGEN technology purifies drinking water, mixes it with salt, and transfers it to a suitable bag to deliver a sterile normal saline solution. Operational constraints such as mass limitations and lack of refrigeration may limit the type and volume of such fluids that can be carried onboard the spacecraft. In addition, most medical fluids have a shelf life that is shorter than some mission durations. Consequently, the objective of the IVGEN experiment was to develop, design, and validate the necessary methodology to purify spacecraft potable water into a normal saline solution, thus reducing the amount of IV fluids that are included in the launch manifest. As currently conceived, an IVGEN system for a space exploration mission would consist of an accumulator, a purifier, a mixing assembly, a salt bag, and a sterile bag. The accumulator is used to transfer a measured amount of drinking water from the spacecraft to the purifier. The purifier uses filters to separate any air bubbles that may have gotten trapped during the drinking water transfer from flowing through a high-quality deionizing cartridge that removes the impurities in

  1. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects.

    PubMed

    Bardak, Handan; Gunay, Murat; Mumcu, Ugur; Bardak, Yavuz

    2016-01-01

    No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p > 0.05). A significant increase was observed in TF and HOA measurements following coffee intake (p = 0.029 and p = 0.009, resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects. PMID:27437402

  2. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects

    PubMed Central

    Bardak, Handan; Gunay, Murat; Mumcu, Ugur; Bardak, Yavuz

    2016-01-01

    No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p > 0.05). A significant increase was observed in TF and HOA measurements following coffee intake (p = 0.029 and p = 0.009, resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects. PMID:27437402

  3. [Pharmacokinetics of cefixime in healthy volunteers after a single oral administration of 200 mg].

    PubMed

    Montay, G; Le Liboux, A; Thebault, J J; Roche, G; Frydman, A; Gaillot, J

    1989-10-11

    The antibacterial activity of cefixime is identical with that of parenteral third generation cephalosporins. Its kinetics were studied in 24 healthy male volunteers who received one single 200 mg tablet. Cmax was 3.25 mg/l and Tmax was 4 h. After 12 hours, serum concentrations were still as high as 0.70 mg/l. Half-life was 3.3 h and urinary excretion was not predominant. Thus, cefixime was characterized by its relatively long serum half-life as compared with other cephalosporins. Despite some degree of individual variations, serum and urine concentrations of the antibiotic remained for 12 hours above the MIC of susceptible pathogens. PMID:2530537

  4. Intravenous acetaminophen use in pediatrics.

    PubMed

    Shastri, Nirav

    2015-06-01

    Acetaminophen is a commonly used pediatric medication that has recently been approved for intravenous use in the United States. The purpose of this article was to review the pharmacodynamics, indications, contraindications, and precautions for the use of intravenous acetaminophen in pediatrics. PMID:26035501

  5. A SINGLE HIGH DOSE OF METHAMPHETAMINE INCREASES COCAINE SELF-ADMINISTRATION BY DEPLETION OF STRIATAL DOPAMINE IN RATS

    PubMed Central

    XI, Z.-X.; KLEITZ, H. K.; DENG, X.; LADENHEIM, B.; PENG, X.-Q.; LI, X.; GARDNER, E. L.; STEIN, E. A.; CADET, J. L.

    2013-01-01

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10–20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kg×1 or 10 mg/kg/2 h×4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in “breakpoint” levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10–20 mg/kg) produced large DA release (4000%–6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  6. A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats.

    PubMed

    Xi, Z-X; Kleitz, H K; Deng, X; Ladenheim, B; Peng, X-Q; Li, X; Gardner, E L; Stein, E A; Cadet, J L

    2009-06-30

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10-20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kgx1 or 10 mg/kg/2 hx4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in "break-point" levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10-20 mg/kg) produced large DA release (4000%-6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenyla