Administration costs of intravenous biologic drugs for rheumatoid arthritis.

PubMed

Soini, Erkki J; Leussu, Miina; Hallinen, Taru

2013-01-01

Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs with published cost estimates. Cost price data for the infusions and drugs were systematically collected from the 2011 Finnish price lists. All Finnish hospitals with available price lists were included. Drug administration and total costs (administration cost + drug price) per infusion were analysed separately from the public health care payer's perspective. Further adjustments for drug brand, dose, and hospital type were done using regression methods in order to improve the comparability between drugs. Annual expected drug administration and total costs were estimated. A literature search not limited to RA was performed to obtain the per infusion administration cost estimates used in publications. The published costs were converted to Finnish values using base-year purchasing power parities and indexing to the year 2011. Information from 19 (95%) health districts was obtained (107 analysable prices out of 176 observations). The average drug administration cost for infliximab, rituximab, abatacept, and tocilizumab infusion in RA were €355.91; €561.21; €334.00; and €293.96, respectively. The regression-adjusted (dose, hospital type; using semi-log ordinary least squares) mean administration costs for infliximab and rituximab infusions in RA were €289.12 (95% CI €222.61-375.48) and €542.28 (95% CI €307.23-957.09). The respective expected annual drug administration costs were €2312.96 for infliximab during the first year, €1879.28 for infliximab during the forthcoming years, and �

Distribution of creatinine following intravenous and oral administration to rats.

PubMed

Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

1981-05-01

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Three-dimensional visualization of endolymphatic hydrops after intravenous administration of single-dose gadodiamide.

PubMed

Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Bokura, Kiminori; Sone, Michihiko; Nakashima, Tsutomu

2013-01-01

Endolymphatic hydrops can be visualized with high contrast-to-noise ratio even after intravenous injection of single-dose gadolinium-based contrast material (IV-SD-GBCM) using HYDROPS-Mi2 images. We applied 3-dimensional rendering software to process HYDROPS-Mi2 images of 15 ears with and without suspected Ménière's disease and separately visualized the volumes of endo- and perilymph in patients with Ménière's disease even after IV-SD-GBCM. Such dimensional visualization will aid understanding of the pathophysiology of Ménière's disease.

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

USDA-ARS?s Scientific Manuscript database

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...

Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen.

PubMed

Singla, Neil K; Parulan, Cherri; Samson, Roselle; Hutchinson, Joel; Bushnell, Rick; Beja, Evelyn G; Ang, Robert; Royal, Mike A

2012-09-01

This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen. Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV(®) ; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol(®) 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall(®) 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg. Acetaminophen plasma and CSF levels were obtained at T0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 6 hours. IV acetaminophen showed earlier and higher plasma and CSF levels compared with PO or PR administration. CSF bioavailability over 6 hours (AUC(0-6)) for IV, PO, and PR 1 g was 24.9, 14.2, and 10.3 μg·h/mL, respectively. No treatment-related adverse events were reported. One subject was replaced because of premature failure of his lumbar spinal catheter. The mean CSF level in the IV group was similar to plasma from 3 to 4 hours and higher from 4 hours on. Absorption phase, variability in plasma, and CSF were greater in PO and PR groups than variability with IV administration. These results demonstrate that earlier and greater CSF penetration occurs as a result of the earlier and higher plasma peak with IV administration compared with PO or PR. © 2012 Lotus Clinical Research, LLC. Pain Practice © 2012 World Institute of Pain.

Comparison between topical and intravenous administration of tranexamic acid in primary total hip arthroplasty.

PubMed

Ueno, Masaya; Sonohata, Motoki; Fukumori, Norio; Kawano, Shunsuke; Kitajima, Masaru; Mawatari, Masaaki

2016-01-01

Tranexamic acid has been reported to be safer with topical administration than with intravenous administration in total knee arthroplasty. However, the most effective administration route of tranexamic acid in total hip arthroplasty remains controversial. This study compared the effectiveness of topical tranexamic acid administration with that of intravenous tranexamic acid administration in total hip arthroplasty. We retrospectively examined the medical records of 886 patients with osteoarthritis of the hip joint, who had undergone unilateral primary total hip arthroplasty. The patients were divided into a control group (n = 302; did not receive tranexamic acid), topical group (n = 265; topically administered 2 g tranexamic acid in 30 mL normal saline via drain tubes placed in the joint before wound closure along with posterior soft tissue repair), and intravenous group (n = 319; intravenously administered 1 g tranexamic acid before skin incision along with posterior soft tissue repair). Data on blood loss, hemoglobin levels, transfusion rates, and occurrence of deep vein thrombosis and pulmonary embolization were collected. The mean operation times were approximately 40 min in all of the groups. The operation time and intra-operative blood loss were significantly lower in the control group than in the topical and intravenous groups. However, the post-operative blood loss, total blood loss, and decrease in the hemoglobin level were significantly higher in the control group than in the topical and intravenous groups. There were no significant differences in terms of blood loss and systemic complications between the tranexamic acid administration methods. Tranexamic acid reduces both post-operative and total blood loss in total hip arthroplasty. Moreover, a lower amount of tranexamic acid can be used to reduce blood loss in total hip arthroplasty with intravenous tranexamic acid administration than with topical tranexamic acid administration. Therefore, we

The pathological anatomy of acute experimental baryllium poisoning peripheral blood changes resulting from intravenous administration of beryllium sulphate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, J.E.

1947-09-01

The lesions produced in the organs following a single intravenous administration of hydrated beryllium sulfate are described. The lesions of the lungs and eyes of animals exposed to the above compound are reviewed. When the baryllium sulfate is given intravenously, midsonal focal necrosis of the liver cells, necrosis of cells of the distal one-third of the proximal convoluted tubules of the kidney and generative changes in the cells of the hemopoietic system are produced. Following exposure of animals to beryllium sulfate dust (100 mg/m{sup 3}, 8 hours daily for eleven days), inflammatory pulmonary lesions are produced which vary in intensitymore » with different species. Pulmonary edema, a terminal bronchitis, and focal atelectasis are the most commonly observed lesions. The eyes of some species exposed to this dust develop conjunctivitis, heratitis, and corneal ulcers. Following a single intravenous administration of beryllium sulfate, rather sharp changes occur in the elements of the peripheral blood. These consist of a secondary anemia (probably resulting from intravascular lysis of red cells), a leukocytosis, and an increase in the number of circulating platelets. 29 figs.« less

Catheter indwell time and phlebitis development during peripheral intravenous catheter administration.

PubMed

Pasalioglu, Kadriye Burcu; Kaya, Hatice

2014-07-01

Intravenous catheters have been indispensable tools of modern medicine. Although intravenous applications can be used for a multitude of purposes, these applications may cause complications, some of which have serious effects. Of these complications, the most commonly observed is phlebitis. This study was conducted to determine the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. This study determined the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. The study included a total of 103 individuals who were administered 439 catheters and satisfied the study enrollment criteria at one infectious diseases clinic in Istanbul/Turkey. Data were compiled from Patient Information Forms, Peripheral Intravenous Catheter and Therapy Information Forms, reported grades based on the Visual Infusion Phlebitis Assessment Scale, and Peripheral Intravenous Catheter Nurse Observation Forms. The data were analyzed using SPSS. Results : The mean patient age was 53.75±15.54 (standard deviation) years, and 59.2% of the study participants were men. Phlebitis was detected in 41.2% of peripheral intravenous catheters, and the rate decreased with increased catheter indwell time. Analyses showed that catheter indwell time, antibiotic usage, sex, and catheterization sites were significantly associated with development of phlebitis. The results of this study show that catheters can be used for longer periods of time when administered under optimal conditions and with appropriate surveillance.

Disposition of styrene-acrylonitrile (SAN) trimer in female rats: single dose intravenous and gavage studies.

PubMed

Gargas, Michael L; Collins, Brad; Fennell, Timothy R; Gaudette, Norman F; Sweeney, Lisa M

2008-04-21

Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano-1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [3H]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T1/2 approximately 1h) following a single intravenous dose and following single oral doses (T1/2 approximately 3-4h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2h after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats.

Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects.

PubMed

Recordati, Camilla; De Maglie, Marcella; Bianchessi, Silvia; Argentiere, Simona; Cella, Claudia; Mattiello, Silvana; Cubadda, Francesco; Aureli, Federica; D'Amato, Marilena; Raggi, Andrea; Lenardi, Cristina; Milani, Paolo; Scanziani, Eugenio

2016-02-29

Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue

[Pharmacokinetics of α-asarone after intranasal and intravenous administration with PLA-α-asarone nanoparticles].

PubMed

Lu, Jin; Guo, Li-Wei; Fu, Ting-Ming; Zhu, Guo-Long; Dai, Zhen-Nan; Zhan, Guan-Jun; Chen, Li-Li

2017-06-01

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration. Copyright© by the Chinese Pharmaceutical Association.

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

Catheter indwell time and phlebitis development during peripheral intravenous catheter administration

PubMed Central

Pasalioglu, Kadriye Burcu; Kaya, Hatice

2014-01-01

Objective: Intravenous catheters have been indispensable tools of modern medicine. Although intravenous applications can be used for a multitude of purposes, these applications may cause complications, some of which have serious effects. Of these complications, the most commonly observed is phlebitis. This study was conducted to determine the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. Methods: This study determined the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. The study included a total of 103 individuals who were administered 439 catheters and satisfied the study enrollment criteria at one infectious diseases clinic in Istanbul/Turkey. Data were compiled from Patient Information Forms, Peripheral Intravenous Catheter and Therapy Information Forms, reported grades based on the Visual Infusion Phlebitis Assessment Scale, and Peripheral Intravenous Catheter Nurse Observation Forms. The data were analyzed using SPSS. Results : The mean patient age was 53.75±15.54 (standard deviation) years, and 59.2% of the study participants were men. Phlebitis was detected in 41.2% of peripheral intravenous catheters, and the rate decreased with increased catheter indwell time. Analyses showed that catheter indwell time, antibiotic usage, sex, and catheterization sites were significantly associated with development of phlebitis. Conclusion: The results of this study show that catheters can be used for longer periods of time when administered under optimal conditions and with appropriate surveillance. PMID:25097505

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

The assesment of effectiveness of plasmonic resonance photothermal therapy in tumor-bearing rats after multiple intravenous administration of gold nanorods

NASA Astrophysics Data System (ADS)

Bucharskaya, Alla B.; Maslyakova, Galina N.; Navolokin, Nikita A.; Terentyuk, Georgy S.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, V. V.

2017-03-01

To assess the effectiveness of plasmonic photothermal therapy (PPT) multiple intravenous strategy of gold nanorods (GNRs) administration was used before laser exposure. The model of alveolar liver cancer PC-1 was used in male outbred albino rats, which were intravenously administrated by single and multiple injections of GNRs and then were treated by PPT. The gold dosage was 400 μg (single injection group), 800 μg (double injection group), 1200 μg (triple injection group), and absorption maximum of gold nanorods suspension was at the wavelength of 808 nm. 24 hours after last injection the tumors were irradiated by the 808-nm diode laser during 15 min at power density 2.3 W/cm2. Temperature control of the tumor heating was provided by IR imager. 24 hours after the PPT the half of animals from each group was withdrawn from the experiments and the sampling tumor tissue for morphological study was performed. In survived animals the growth of tumors was evaluated during 21 days after the PPT. The antitumor effects of PPT after triple intravenous injection were comparable with those obtained at direct intratumoral administration of similar total dose of GNRs. The effectiveness of PPT depended on gold accumulation in tumor, probably, due to sufficient vascularization of tumor tissue.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats].

PubMed

Yahara, I; Furukawa, H; Sato, K; Nishimura, K; Harihara, A; Yabuuchi, K; Miyauchi, H; Kii, Y; Muraoka, Y; Kitamura, T; Kato, I

2001-05-01

A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred. Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration. These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration. Body weights increased favorably, and no S-1090-related pathological changes were observed. The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg. Single intravenous dose toxicity study of S-1090-Na No deaths occurred. The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course. These signs disappeared by 4 hr after administration. Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats. Body weights increased favorably. In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed. The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.

Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

PubMed

Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

2013-03-01

Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

Pharmacokinetics of meloxicam after intravenous, intramuscular and oral administration of a single dose to African grey parrots (Psittacus erithacus).

PubMed

Montesinos, A; Ardiaca, M; Gilabert, J A; Bonvehí, C; Oros, J; Encinas, T

2017-06-01

Meloxicam is a nonsteroidal anti-inflammatory drug commonly used in avian species. In this study, the pharmacokinetic parameters for meloxicam were determined following single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of the drug (1 mg/kg·b.w.) in adult African grey parrots (Psittacus erithacus; n = 6). Serial plasma samples were collected and meloxicam concentrations were determined using a validated high-performance liquid chromatography assay. A noncompartmental pharmacokinetic analysis was performed. No undesirable side effects were observed during the study. After i.v. administration, the volume of distribution, clearance and elimination half-life were 90.6 ± 4.1 mL/kg, 2.18 ± 0.25 mL/h/kg and 31.4 ± 4.6 h, respectively. The peak mean ± SD plasma concentration was 8.32 ± 0.95 μg/mL at 30 min after i.m. administration. Oral administration resulted in a slower absorption (t max  = 13.2 ± 3.5 h; C max  = 4.69 ± 0.75 μg/mL) and a lower bioavailability (38.1 ± 3.6%) than for i.m. (78.4 ± 5.5%) route. At 24 h, concentrations were 5.90 ± 0.28 μg/mL for i.v., 4.59 ± 0.36 μg/mL for i.m. and 3.21 ± 0.34 μg/mL for p.o. administrations and were higher than those published for Hispaniolan Amazon parrots at 12 h with predicted analgesic effects. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

2015-07-01

To investigate the effects of intravenous infliximab in preventing the formation of peritoneal adhesions in an animal model of rat. 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. 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). Administration of intravenous infliximab after intraabdominal surgicalprocedures would not prevent the formation of peritoneal adhesions in animal model of albino rat.

Effects of albendazole nanoparticles in mice with hepatic echinococosis: Portal vein cannulation versus intravenous administration.

PubMed

Zhu, Di-Wen; Zhang, Ming-Xing; Bao, Ying-Jun; Gu, Jun-Peng; Ji, Wei-Zheng; Zhang, Hai-Xiao; Ren, Wei-Xin

2015-07-01

To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group. Copyright © 2015 Elsevier Inc. All rights reserved.

Severe hypophosphataemia after intravenous iron administration

PubMed Central

Anand, Gurpreet; Schmid, Christoph

2017-01-01

Iron deficiency is common and can be effectively treated with parenteral iron infusion. We report a case of an iron-deficient and vitamin D-deficient woman who developed severe symptomatic hypophosphataemia following intravenous ferric carboxymaltose administration. We stress the need of increased awareness of this potential complication among physicians. Patients should be informed of this complication and instructed to report for follow-up if they experience new musculoskeletal symptoms or worsening of tiredness. As severe hypophosphataemia is usually symptomatic, we recommend screening symptomatic patients for this complication. Recognising and treating the possible exacerbating factors, especially vitamin D deficiency, might be a simple measure to mitigate this complication. PMID:28289000

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

Neurotoxicity of misonidazole in rats following intravenous administration.

PubMed

Graziano, M J; Henck, J W; Meierhenry, E F; Gough, A W

1996-06-01

Misonidazole is a hypoxic cell radiosensitizer that induces a peripheral neuropathy in humans after exceeding a schedule-dependent cumulative threshold dose. Clinical studies of misonidazole have been conducted using oral administration, whereas most other radiosensitizers have been administered intravenously. Since route of exposure can potentially influence the toxicity of xenobiotics, the objective of this study was to assess the neurotoxicity of misonidazole in rats following intravenous dosing using a battery of routine clinical, neurofunctional, biochemical, and histopathologic screening methods. Male Sprague-Dawley rats were administered intravenous doses of misonidazole at 0 (vehicle control), 100, 200, 300, or 400 mg kg-1 once per day, 5 days per week, for 2 weeks. Animals were evaluated for neurofunctional and pathological changes following termination of treatment (Days 15-17) and at the end of a 4 week observation period (Days 43-45). During the dosing phase, hypoactivity, salivation, rhinorrhea, chromodacryorrhea, rough pelage and ataxia were observed at 400 mg kg-1, and body weight gain of the 300 and 400 mg kg-1 groups was significantly decreased relative to the vehicle controls by 24% and 49%, respectively. Corresponding reductions in food consumption were 8% and 23%, respectively. Although most 400 mg kg-1 animals appeared normal on Day 15 prior to the neurofunctional evaluations, rotorod testing precipitated a number of clinical signs including: ataxia, impaired righting reflex, excessive rearing, tremors, vocalization, circling, head jerking, excessive sniffing and hyperactivity. All of these animals recovered and appeared normal from Day 17 through study termination. There were no treatment-related effects on motor activity, acoustic startle response, rotorod performance, forelimb group strength, toe and tail pinch reflexes, tibial nerve beta-glucuronidase activity or tail nerve conduction velocity. Although hindlimb grip strength of the 400 mg

Behaviour of Standard Gravity-fed Administration Sets Used for Intravenous Infusion

PubMed Central

Flack, F. C.; Whyte, T. D.

1974-01-01

The major factor influencing drip rate during intravenous infusion using a standard administration set is the variation in the venous pressure of the patient. Creep in the plastic material, though present, is shown to be unimportant. For steady and accurate infusion it is necessary to provide the ordinary gravity-fed administration set with some form of servo-control mechanism. PMID:4412178

[Antidote against local anaesthetic intoxication: new use of lipid emulsion for intravenous administration].

PubMed

ter Horst, Maarten; Tjiang, Gilbert C H; Luitwieler, Ronald L; van Velzen, Chris; Stolker, Robert Jan; de Quelerij, Marcel

2010-01-01

Local anaesthetics are routinely used for several indications, but despite local administration their use may lead to systemic toxicity. The symptoms include numbness of the tongue, dizziness, tinnitus, visual disturbances, muscle spasms, convulsions, coma, and respiratory and cardiac arrest. Recently, an intravenous lipid emulsion was reported to act as a novel potential antidote for systemic toxicity due to local anaesthetics. We describe the application of this lipid emulsion in a 27-year-old patient with generalized seizures and coma due to local anaesthetic toxicity. She recovered quickly and was responsive again 10 minutes after the intravenous administration of the lipid emulsion.

Severe hypophosphataemia after intravenous iron administration.

PubMed

Anand, Gurpreet; Schmid, Christoph

2017-03-13

Iron deficiency is common and can be effectively treated with parenteral iron infusion. We report a case of an iron-deficient and vitamin D-deficient woman who developed severe symptomatic hypophosphataemia following intravenous ferric carboxymaltose administration. We stress the need of increased awareness of this potential complication among physicians. Patients should be informed of this complication and instructed to report for follow-up if they experience new musculoskeletal symptoms or worsening of tiredness. As severe hypophosphataemia is usually symptomatic, we recommend screening symptomatic patients for this complication. Recognising and treating the possible exacerbating factors, especially vitamin D deficiency, might be a simple measure to mitigate this complication. 2017 BMJ Publishing Group Ltd.

Intravenous Alcohol Self-Administration in the P Rat

PubMed Central

Windisch, Kyle A.; Kosobud, Ann E. K.; Czachowski, Cristine L.

2014-01-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding “non-pharmacological” effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol’s effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous

Intravenous alcohol self-administration in the P rat.

PubMed

Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

2014-08-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol

[Single intravenous tranexamic acid dose to reduce blood loss in primary total knee replacement].

PubMed

Sanz-Reig, J; Parra Ruiz, B; Ferrández Martínez, J; Martínez López, J F

2016-01-01

To evaluate the effectiveness and safety of a single intravenous dose of tranexamic acid in order to reduce blood loss in total knee replacement. Prospective observational study of the administration of tranexamic acid in patients undergoing primary total knee arthroplasty from November 2013 to February 2015, in which an autologous blood recovery system was used. The study included 98 patients, distributed into two groups of 49 patients according to whether or not they received intravenous tranexamic acid. The primary endpoint was the number of patients requiring autologous transfusion from the recovery system autologous blood recovery system. No drop-outs were recorded during follow-up. There were no significant differences between groups as regards the preoperative and hospital variables. The mean preoperative haemoglobin and haematocrit at 24 and 48 hours postoperatively were similar in both groups. The average volume of bleeding in the autologous blood recovery system and estimated average blood loss was lower in patients who had been administered tranexamic acid, with significant differences. No patients in the group that was administered tranexamic acid required blood autotransfusion. The transfusion rate was zero in the two groups. No adverse events related to the administration of tranexamic acid were recorded. Intravenous administration of tranexamic acid, according to the described protocol, has presented a non-autotransfusion or allo-transfusion rate of 100%, with no increased incidence of thrombotic events. Thus, its use in this group of patients is recommended. The indication should be individualized, its use justified in the patient medical records, and informed consent is mandatory. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients.

PubMed Central

Schaad, U B; Casey, P A; Cooper, D L

1983-01-01

Pharmacokinetics of a parenteral formulation comprised of 5 parts of amoxicillin and 1 part of clavulanic acid were determined in 12 pediatric patients, 2 to 14 years of age. A single dose amounting to 25 mg of amoxicillin and 5 mg of clavulanic acid per kg of body weight was infused intravenously over 2 min. Mean plasma concentrations 5 min after dosing were 89.4 micrograms of amoxicillin per ml and 19.5 micrograms of clavulanic acid per ml. Terminal phase plasma half-lives were 1.2 and 0.8 h, respectively. The data acquired in this study indicate that amoxicillin and clavulanic acid are pharmacokinetically compatible. Moreover, taken with assessment of microbiological activities by others, the present data suggest that intravenous administration of 25 mg of amoxicillin plus 5 mg of clavulanic acid per kg every 6 h is a reasonable starting regimen for assessing the activity of the combined drug formulation in noninvasive childhood diseases caused by Haemophilus influenzae, Staphylococcus aureus, Streptococci spp., Neisseria spp., Branhamella catarrhalis, and other susceptible organisms. Images PMID:6838187

Single-dose pharmacokinetics of intravenous clavulanic acid with amoxicillin in pediatric patients.

PubMed

Schaad, U B; Casey, P A; Cooper, D L

1983-02-01

Pharmacokinetics of a parenteral formulation comprised of 5 parts of amoxicillin and 1 part of clavulanic acid were determined in 12 pediatric patients, 2 to 14 years of age. A single dose amounting to 25 mg of amoxicillin and 5 mg of clavulanic acid per kg of body weight was infused intravenously over 2 min. Mean plasma concentrations 5 min after dosing were 89.4 micrograms of amoxicillin per ml and 19.5 micrograms of clavulanic acid per ml. Terminal phase plasma half-lives were 1.2 and 0.8 h, respectively. The data acquired in this study indicate that amoxicillin and clavulanic acid are pharmacokinetically compatible. Moreover, taken with assessment of microbiological activities by others, the present data suggest that intravenous administration of 25 mg of amoxicillin plus 5 mg of clavulanic acid per kg every 6 h is a reasonable starting regimen for assessing the activity of the combined drug formulation in noninvasive childhood diseases caused by Haemophilus influenzae, Staphylococcus aureus, Streptococci spp., Neisseria spp., Branhamella catarrhalis, and other susceptible organisms.

Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats.

PubMed

Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

2016-12-01

The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen. © The Author(s) 2015.

Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences.

PubMed

Cosgrove, Kelly P; Hunter, Robb G; Carroll, Marilyn E

2002-10-01

This experiment examines the effect of access to a running-wheel on intravenous cocaine self-administration in male and female rats. Rats maintained at 85% of their free-feeding body weight were first exposed to the running-wheel alone during the 6-h sessions until behavior stabilized for 14 days. Intravenous cannulae were then implanted, and the rats were trained to self-administer a low dose of cocaine (0.2 mg/kg) under a fixed-ratio (FR 1) schedule during the 6-h sessions, while the wheel remained inactive and cocaine self-administration stabilized (cocaine-only condition). Next, the wheel access and cocaine self-administration were concurrently available followed by a period of cocaine-only. Behavior was allowed to stabilize for 10 days at each phase. During wheel access, cocaine infusions decreased by 21.9% in males and 70.6% in females compared to the cocaine-only condition; the effect was statistically significant in females. Infusions increased to baseline levels when wheel access was terminated. When cocaine infusions were concurrently available, wheel revolutions were reduced by 63.7% and 61.5% in males and females, respectively, compared to the wheel-only condition. This result did not differ due to sex, but it was statistically significant when data from males and females were combined. These results indicate that wheel-running activity had a greater suppressant effect on cocaine self-administration in females than in males, and in females, wheel-running and cocaine self-administration are substitutable as reinforcers.

Three insulation methods to minimize intravenous fluid administration set heat loss.

PubMed

Piek, Richardt; Stein, Christopher

2013-01-01

To assess the effect of three methods for insulating an intravenous (IV) fluid administration set on the temperature of warmed fluid delivered rapidly in a cold environment. The three chosen techniques for insulation of the IV fluid administration set involved enclosing the tubing of the set in 1) a cotton conforming bandage, 2) a reflective emergency blanket, and 3) a combination of technique 2 followed by technique 1. Intravenous fluid warmed to 44°C was infused through a 20-drop/mL 180-cm-long fluid administration set in a controlled environmental temperature of 5°C. Temperatures in the IV fluid bag, the distal end of the fluid administration set, and the environment were continuously measured with resistance thermosensors. Twenty repetitions were performed in four conditions, namely, a control condition (with no insulation) and the three different insulation methods described above. One-way analysis of variance was used to assess the mean difference in temperature between the IV fluid bag and the distal fluid administration set under the four conditions. In the control condition, a mean of 5.28°C was lost between the IV fluid bag and the distal end of the fluid administration set. There was a significant difference found between the four conditions (p < 0.001). A mean of 3.53°C was lost between the IV fluid bag and the distal end of the fluid administration set for both the bandage and reflective emergency blanket, and a mean of 3.06°C was lost when the two methods were combined. Using inexpensive and readily available materials to insulate a fluid administration set can result in a reduction of heat loss in rapidly infused, warmed IV fluid in a cold environment.

Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration.

PubMed

Li, Guanghui; Yang, Fan; He, Limin; Ding, Huanzhong; Sun, Na; Liu, Yingchun; Liu, Yiming; Shan, Qi; Li, Yafei; Zeng, Zhenling

2012-12-01

Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose of 10 mg kg(-1) bodyweight. After both administrations, MEQ and five of its metabolites were quantified, except M4, whereas M1 and M2 were the predominant ones. The areas under the concentration-time curves (h ng mL(-1)) of MEQ, M1, M2, M3, M5 and M10 after i.v. administration were 7559±495, 6354±2761, 5586±2337, 1034±160, 2370±791 and 1813±622, respectively, whereas after p.o. administration, remained as 2809±40, 4361±3544, 4351±1046, 1444±814, 3864±305 and 1213±569, respectively. The elimination half-lives (h) of these compounds after i.v. administration were 3.48±0.80, 4.20±0.76, 6.25±2.41, 4.77±1.54, 4.69±1.62 and 16.89±5.15, respectively, and were 3.21±0.40, 3.66±1.06, 4.20±1.03, 8.91±5.99, 4.20±2.02 and 20.84±10.85 after p.o. administration, respectively. After p.o. administration, the bioavailability of MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats and rapidly absorbed after p.o. administration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

PubMed

Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

2018-03-01

Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

Vedolizumab Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability Following Administration of a Single, Ascending, Intravenous Dose to Healthy Volunteers.

PubMed

Rosario, Maria; Wyant, Timothy; Leach, Timothy; Sankoh, Serap; Scholz, Catherine; Parikh, Asit; Fox, Irving; Feagan, Brian G

2016-11-01

Vedolizumab, a humanized monoclonal antibody against the α 4 β 7 integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn's disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab were evaluated in healthy volunteers. Forty-nine participants (in five cohorts) were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of either vedolizumab (0.2, 0.5, 2.0, 6.0, or 10.0 mg/kg) or placebo. Blood samples were collected for measurement of vedolizumab serum concentrations and α 4 β 7 saturation on peripheral blood lymphocytes by vedolizumab. Pharmacokinetic parameters were computed using a non-compartmental approach. Adverse events were monitored. Vedolizumab maximum observed serum concentration (C max ) demonstrated dose proportionality over the dose range tested. Greater than dose-proportional increases in area under the serum concentration-time curve from time 0 to infinity (AUC 0-inf ) and shorter terminal elimination half-life (t 1/2 ) were observed from 0.2 to 2.0 mg/kg, suggestive of nonlinear pharmacokinetics at lower doses. At doses higher than 2.0 mg/kg, these parameters increased dose proportionally. Saturation of α 4 β 7 was at or near maximal levels (>90 %) at all doses and time points when vedolizumab was measurable in serum. A total of 21 of 39 (54 %) vedolizumab-treated participants were anti-drug antibody (ADA) positive, and 11 (28 %) were persistently ADA positive. Overall, no adverse event signals, including serious infections or malignancies, were apparent. Vedolizumab exhibited target-mediated disposition, characterized by a rapid, saturable, nonlinear elimination process at low concentrations and a slower linear elimination process at higher concentrations. Nearly complete α 4 β 7 saturation was observed at all doses. A single intravenous infusion of vedolizumab

Single jugular vein cannulated rats may not be suitable for intravenous pharmacokinetic screening of high logP compounds.

PubMed

Gaud, Nilesh; Kumar, Anoop; Matta, Muralikrishna; Kole, Prashant; Sridhar, Srikanth; Mandlekar, Sandhya; Holenarsipur, Vinay K

2017-03-01

Rat is commonly used for pharmacokinetic screening during pharmaceutical lead optimization. To handle the large number of compounds, rats with a single jugular vein cannulation are commonly utilized for intravenous pharmacokinetic studies, where the same cannula is used both for dose administration and blood sampling. We demonstrate that the single cannula method is not suitable for all compounds, especially for high logP compounds. We propose an alternative dual cannulation technique in which two cannulas are placed in the same jugular vein, thus avoiding an additional surgery. Compounds were administered orally or via intravenous infusion to compare PK parameters, including bioavailability, using both procedures. For itraconazole and amiodarone, known to bind to the cannula, the measured plasma exposures were substantially higher in the single cannulated rats than those from dual cannulated rats. Area under the plasma concentration time curve differed by 79% and 74% for itraconazole and amiodarone, respectively. When compared to the single cannulation approach, clearance, volume of distribution and bioavailability determined by dual cannulation were 39%, 60% and 38% higher for itraconazole, and 46%, 34% and 42% higher for amiodarone, respectively. In contrast, all pharmacokinetic parameters were similar between single and dual-cannulated rats for the hydrophilic compound atenolol. Based on these results, we recommend the use of dual cannulated rats for intravenous pharmacokinetic studies when testing a series of hydrophobic compounds that may be prone to non-specific binding to the cannula. If single cannulated model is selected for pharmacokinetic screening, we recommend a bridging study with dual cannulated rats with representative compounds of a given chemical series. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacokinetics and tolerability of intravenous ibuprofen injection in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
.

PubMed

Zhou, Huili; Xu, Wei; Wu, Guolan; Wu, Lihua; Shentu, Jianzhong; Pan, Zhengfei; Hu, Shuai; Liu, Yang

2016-11-01

Recently a formulation of intravenous (IV) ibuprofen was developed in China for management of mild to moderate pain in patients who could not take oral medications or where intravenous administration was preferable. The aim of this study was to evaluate the pharmacokinetic properties and tolerability of single and multiple doses of ibuprofen injection in healthy Chinese volunteers. This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. In the single-dose phase, subjects were randomized to receive a single dose of ibuprofen injection 0.2, 0.4, or 0.8 g administered as a 30-minute IV infusion with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 12.5 hours after drug administration and were analyzed using a validated LC-MS/MS method. In the multiple-dose phase, subjects received 0.4 g ibuprofen every 6 hours for 9 doses. Blood samples were obtained before the 7^th, 8^th, and 9^th administration to determine the C_min at steady state; on the 9^th intravenous administration, blood samples were also collected for 12.5 hours after drug administration. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). A total of 12 healthy male (n = 6) and female (n = 6) Chinese volunteers were enrolled and completed the trial. After IV administration of single dose, the mean (SD) C_max value increased from 35.77 (6.98) to 117.12 (19.78) µg/mL, and the mean (SD) AUC_0-t value increased from 67.63 (10.30) to 230.50 (33.55) µg×h/mL in the range of 0.2-g to 0.8-g dose. The terminal half-life in plasma was ~ 2.0 hours. After IV administration of 9 doses of ibuprofen 400 mg every 6 hours, the mean (SD) C_max was 66.49 (8.49) µg/mL, the AUC_0-t was 135.65 (26.91) µg×h/mL, the t₁

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.

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

Pharmacokinetics of vanadium in humans after intravenous administration of a vanadium containing albumin solution

PubMed Central

Heinemann, Günter; Fichtl, Burckhard; Vogt, Wolfgang

2003-01-01

Aims Vanadium is currently undergoing clinical trials as an oral drug in patients with noninsulin-dependent diabetes mellitus. Furthermore, vanadium occurs in elevated concentrations in the blood of patients receiving intravenous albumin solutions containing large amounts of the metal ion as an impurity. The present study was performed to examine the pharmacokinetics of vanadium in humans following a single intravenous (i.v.) dose of a commercial albumin solution containing a high amount of vanadium. Methods The study was conducted in five healthy volunteer subjects who received intravenously 90 ml of a commercial 20% albumin infusion solution containing 47.6 µg vanadium as an impurity. Vanadium concentrations in serum and urine were determined by electrothermal atomic absorption spectrometry. Results Vanadium serum concentrations after i.v. administration were measured for 31 days. The data could be fitted by a triexponential function corresponding formally to a three-compartment model. There was an initial rapid decrease in serum concentrations with half-lives of 1.2 and 26 h. This was followed by a long-terminal half-life time of 10 days. The terminal phase accounted for about 80% of the total area under the serum concentration-time curve (AUC). The mean apparent volume of distribution of the central compartment was found to be 10 l. The volume of distribution at steady state was 54 l, and total clearance was 0.15 l h−1. Vanadium was mainly excreted by the kidneys. About 52% of the dose was recovered in the urine after 12 days. Conclusions This study provides data on vanadium pharmacokinetics in healthy humans. PMID:12630973

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

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

PubMed

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.

Comparison of intracoronary versus intravenous administration of adenosine for measurement of coronary fractional flow reserve.

PubMed

Schlundt, Christian; Bietau, Christian; Klinghammer, Lutz; Wiedemann, Ricarda; Rittger, Harald; Ludwig, Josef; Achenbach, Stephan

2015-05-01

Measurement of fractional flow reserve (FFR) constitutes the current gold standard to evaluate the hemodynamic significance of coronary stenoses. Limited data validate the intracoronary application of adenosine against standard intravenous infusion. We systematically compared FFR measurements during intracoronary and intravenous application of adenosine about agreement and reproducibility. We included 114 patients with an intermediate degree of stenosis in coronary angiography. Two FFR measurements were performed during intracoronary bolus injection (40 μg for the right and 80 μg for the left coronary artery, FFRic), and 2 FFR measurements during continuous intravenous infusion of adenosine (140 μg/kg per minute, FFRiv). FFR value, the time to reach FFR and patient discomfort (on a subjective scale from 0 for no symptoms to 5 for maximal discomfort) were recorded for each measurement. Mean time to FFR was 100 ± 27 s for continuous intravenous infusion versus 23 ± 14 s for intracoronary bolus administration of adenosine (P < 0.001). Reported discomfort after intracoronary application was significantly lower compared with intravenous adenosine (subjective scale > 0 in 35.1% versus 87.7% of the patients; P < 0.001). Correlation between FFRiv and FFRic was extremely close (r = 0.99; P < 0.001) with no systematic bias in Bland-Altman analysis (bias 0.002 [confidence interval, -0.001 to 0.005]) and low intermethod variability (1.56%). Intramethod variability was not different between intravenous and intracoronary administration (1.47% versus 1.33%; P=0.5). Intracoronary bolus injection of adenosine (40 μg for the right and 80 μg for the left coronary artery) yields identical FFR results compared with intravenous infusion (140 μg/kg per minute), while requiring less time and offering superior patient comfort. © 2015 American Heart Association, Inc.

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

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

PubMed

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

2016-03-03

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. 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. 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. 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.

The effect of in-vivo intravenous administration of sodium meglumine diatrizoate on some haematological parameters.

PubMed

Agwu, K K; Mgbor, S; Ogbu, S O I; Okeji, M

2007-01-01

To investigate the in-vivo effects of intravenous administration of sodium meglumine diatrizoate on some haematological parameters in a Nigerian population. Blood samples were collected before and one hour after intravenous injection of sodium-meglumine diatrizoate from 50 subjects undergoing intravenous urography examinations who had no history of and laboratory confirmed diseases that may affect haematological parameters. Standard laboratory methods were used to assay the haemoglobin concentration (Hb), packed cell volume (PCV), total white blood cell (WBC) count and differentials and blood film for any morphological changes in the red blood cells (RBC). Comparisons were made between the mean values of these haematological parameters before and one hour post injection using paired t-test for any statistically significant differences. There were statistically significant reductions in the mean values of Hb concentration and the neutrophil count one hour post injection compared with their pretest values (p < 0.05). The lymphocytes were also significantly increased post injection compared to the pretest values whereas 70% of the erythrocytes were morphologically altered from their approximately 100% normocytic shape at pre-test. Intravenous administration of sodium-meglumine diatrizoate causes in-vivo reduction in Hb concentration and neutrophil count in humans as well as poikilocytosis of the erythrocytes. Some of these effects have the potential of triggering or exacerbating crisis in a sickle cell anaemia subject which is endemic in our locality. Caution should therefore be exercised in the choice and administration of radiological contrast agents to sickle cell subjects. Preparations that are iso-osmolar with plasma and have less probability in precipitating crises should be preferred instead.

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. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

PubMed

Choi, Yi Jeong; Kim, Nam Jun; Zhao, Rong Jie; Kim, Da Hye; Yang, Chae Ha; Kim, Hee Young; Gwak, Young S; Jang, Eun Young; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; Lee, Sang Nam; Lim, Sung Chul; Lee, Bong Hyo

2018-01-01

Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABA A or GABA B receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers.

PubMed

Crevoisier, C; Delisle, M C; Joseph, I; Foletti, G

2003-01-01

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C(max) 11.0 vs. 14.9 ng.ml(-1)) and time to reach maximum concentration (t(max) 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C(max) 9.9 ng.ml(-1); t(max) 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC(0- infinity ) 620 vs. 561 ng.h.ml(-1)). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V(Z)) were 55 ml.min(-1) and 180 liters, respectively. In conclusion, the observed differences in C(max) and t(max) after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients

The Cardiovascular Effect of Single Injection and Toxicologic Effects of Repetitive 2-Week Intravenous Administration of Activin A/BMP-2 Chimera in Beagle Dog.

PubMed

Lee, Jae Hyup; Choe, Senyon; Han, Shihuan

2018-02-01

This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R-R interval, QT interval and QTcV interval on the electrocardiography. Also, when administered AB204 at the doses of 0.25 and 0.5 mg/kg/day via repetitive intravenous injection for 2 weeks, it did not cause any significant changes in general symptoms, weight, food intake, ophthalmologic abnormality, urine, hematology, serum biochemistry, organ weight and autopsy values. Therefore, AB204 did not affect cardiovascular functions including blood pressure, pulse rate and ECG, when administered at the dose of ≤0.32 mg/kg via single intravenous injection in male beagle dogs. When it was administered at the dose of 0.5 mg/kg repetitive intravenous injection for 2 weeks, it did not show any toxicity.

High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats.

PubMed

Cornish, Jennifer L; Clemens, Kelly J; Thompson, Murray R; Callaghan, Paul D; Dawson, Bronwyn; McGregor, Iain S

2008-01-01

Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.

Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.

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 ofmore » 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.« less

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. Copyright © 2015 Elsevier B.V. All rights reserved.

FREE 17-HYDROXYCORTICOSTERIOD CONCENTRATION OF PAROTID FLUID FOLLOWING INTRAVENOUS ADMINISTRATION OF CORTISOL,

DTIC Science & Technology

In an attempt to determine the time required for adrenocortical steroids to pass from the bloodstream to parotid fluid, twenty subjects were given...intravenous injections of cortisol and parotid fluid was collected continuously for 120 minutes after injection. Additional studies were carried out...with intramuscular injections and oral administration of cortisol. The parotid fluid free 17-OHCS mean rose from 3.51 (S.D. = 1.57) to 21.34 (S.D

Pharmacokinetics and bioavailability of denaverine hydrochloride in healthy subjects following intravenous, oral and rectal single doses.

PubMed

Staab, Alexander; Schug, Barbara S; Larsimont, Véronique; Elze, Martina; Thümmler, Daniela; Mutschler, Ernst; Blume, Henning

2003-02-01

The neurotropic-musculotropic spasmolytic agent denaverine hydrochloride is used mainly in the treatment of smooth muscle spasms of the gastrointestinal and urogenital tract. Despite its commercial availability as a solution for intravenous or intramuscular administration (ampoule) and as a suppository formulation, no pharmacokinetic data in man was available to date. Therefore, the objectives of this clinical trial were to determine the basic pharmacokinetic parameters of denaverine after intravenous administration, to assess the feasibility of using the oral route of administration and to characterise the bioavailability of the suppository formulation. To achieve this, healthy subjects received 50 mg denaverine hydrochloride intravenously, orally and rectally in aqueous solutions and rectally as suppository in an open, randomised crossover design. Total body clearance, volume of distribution at steady-state and half-life of denaverine are 5.7 ml/min per kg, 7.1 l/kg and 33.8 h, respectively. The absolute bioavailability after oral administration of an aqueous solution is 37%. First-pass metabolism leading to the formation of N-monodemethyl denaverine was found to be one reason for the incomplete bioavailability after oral administration. Rectal administration of an aqueous solution of denaverine hydrochloride resulted in a decreased rate (median of C(max) ratios: 26%, difference in median t(max) values: 1.9 h) and extent (31%) of bioavailability compared to oral administration. Using the suppository formulation led to a further reduction in rate (median of C(max) ratios: 30%, difference in median t(max) values: 3 h) and extent (42%) of bioavailability compared to the rectal solution.

Pharmacokinetics of 14 C-ortho-phenylphenol following intravenous administration in pigs.

PubMed

Nixon, Emma; Brooks, James D; Routh, Patricia A; Chittenden, Jason T; Baynes, Ronald E

2017-04-01

Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. 14 C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non-compartmental and compartmental pharmacokinetic model approaches. These data fitted a three-compartment model and showed that the half-life of 14 C-OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of 14 C-OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that 14 C-OPP clearance in pigs (2.48 ml h -1  kg -1 ) is less than that in humans (18.87 ml h -1  kg -1 ) and rats (35.51 ml h -1  kg -1 ). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration.

PubMed

Thompson, James D; Kornbrust, Douglas J; Foy, Jeffrey W-D; Solano, Elisabeth C R; Schneider, David J; Feinstein, Elena; Molitoris, Bruce A; Erlich, Shai

2012-08-01

We report the toxicological and pharmacokinetic properties of the synthetic, small interfering RNA I5NP following intravenous administration in rodents and nonhuman primates. I5NP is designed to act via the RNA interference (RNAi) pathway to temporarily inhibit expression of the pro-apoptotic protein p53 and is being developed to protect cells from acute ischemia/reperfusion injuries such as acute kidney injury that can occur during major cardiac surgery and delayed graft function that can occur following renal transplantation. Following intravenous administration, I5NP was very rapidly cleared from plasma was distributed predominantly to the kidney, with very low levels in liver and other tissues. Doses of 800 mg/kg I5NP in rodents, and 1,000 mg/kg I5NP in nonhuman primates, were required to elicit adverse effects, which in the monkey were isolated to direct effects on the blood that included a sub-clinical activation of complement and slightly increased clotting times. In the rat, no additional adverse effects were observed with a rat analogue of I5NP, indicating that the effects likely represent class effects of synthetic RNA duplexes rather than toxicity related to the intended pharmacologic activity of I5NP. Taken together, these data support clinical testing of intravenous administration of I5NP for the preservation of renal function following acute ischemia/reperfusion injury.

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

PubMed

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

2016-01-01

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. 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. 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. 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 a positive financial impact for

Determination of the LD50 of acridine orange via intravenous administration in mice in preparation for clinical application to cancer therapy.

PubMed

Nakamura, Tomoki; Kusuzaki, Katsuyuki; Matsubara, Takao; Matsumine, Akihiko; Asanuma, Kunihiro; Satonaka, Haruhiko; Uchida, Atsumasa; Sudo, Akihiro

2014-01-01

We undertook studies to determine the lethal dose 50 (LD50) of acridine orange (AO) using mice in order to confirm the safety of intravenous administration of AO. We used 40 mice and AO was administered once intravenously. General behavior and mortality were continuously observed for 14 days. At the end of the experiment, all animals were sacrificed for subsequent studies. The LD50 for AO in male and female mice was determined to be 32 mg/kg and 36 mg/kg, respectively. Histopathological abnormalities were observed in only one mouse which died three days after the administration of AO. The other nine mice which died immediately after the administration of AO had no pathological findings in major organs. The clinical use of AO can be kept at 1.0 mg/kg or below and, therefore, intravenous administration of AO might be safe for use as cancer therapy. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

Simple Estimation of the Endolymphatic Volume Ratio after Intravenous Administration of a Single-dose of Gadolinium Contrast

PubMed Central

NAGANAWA, Shinji; KANOU, Mai; OHASHI, Toshio; KUNO, Kayao; SONE, Michihiko

2016-01-01

Purpose: To evaluate the feasibility of a simple estimation for the endolymphatic volume ratio (endolymph volume/total lymph volume = %ELvolume) from an area ratio obtained from only one slice (%EL1slice) or from three slices (%EL3slices). The %ELvolume, calculated from a time-consuming measurement on all magnetic resonance (MR) slices, was compared to the %EL1slice and the %EL3slices. Methods: In 40 ears of 20 patients with a clinical suspicion of endolymphatic hydrops, MR imaging was performed 4 hours after intravenous administration of a single dose of gadolinium-based contrast material (IV-SD-GBCM). Using previously reported HYDROPS2-Mi2 MR imaging, the %ELvolume values in the cochlea and the vestibule were measured separately by two observers. The correlations between the %EL1slice or the %EL3slices and the %ELvolume values were evaluated. Results: A strong linear correlation was observed between the %ELvolume and the %EL3slices or the %EL1slice in the cochlea. The Pearson correlation coefficient (r) was 0.968 (3 slices) and 0.965 (1 slice) for observer A, and 0.968 (3 slices) and 0.964 (1 slice) for observer B (P < 0.001, for all). A strong linear correlation was also observed between the %ELvolume and the %EL3slices or the %EL1slice in the vestibule. The Pearson correlation coefficient (r) was 0.980 (3 slices) and 0.953 (1 slice) for observer A, and 0.979 (3 slices) and 0.952 (1 slice) for observer B (P < 0.001, for all). The high intra-class correlation coefficients (0.991–0.997) between the endolymph volume ratios by two observers were observed in both the cochlea and the vestibule for values of the %ELvolume, the %EL3slices and the %EL1slice. Conclusion: The %ELvolume might be easily estimated from the %EL3slices or the %EL1slice. PMID:27001396

Simple Estimation of the Endolymphatic Volume Ratio after Intravenous Administration of a Single-dose of Gadolinium Contrast.

PubMed

Naganawa, Shinji; Kanou, Mai; Ohashi, Toshio; Kuno, Kayao; Sone, Michihiko

2016-10-11

To evaluate the feasibility of a simple estimation for the endolymphatic volume ratio (endolymph volume/total lymph volume = %EL volume ) from an area ratio obtained from only one slice (%EL 1slice ) or from three slices (%EL 3slices ). The %EL volume, calculated from a time-consuming measurement on all magnetic resonance (MR) slices, was compared to the %EL 1slice and the %EL 3slices . In 40 ears of 20 patients with a clinical suspicion of endolymphatic hydrops, MR imaging was performed 4 hours after intravenous administration of a single dose of gadolinium-based contrast material (IV-SD-GBCM). Using previously reported HYDROPS2-Mi2 MR imaging, the %EL volume values in the cochlea and the vestibule were measured separately by two observers. The correlations between the %EL 1slice or the %EL 3slices and the %EL volume values were evaluated. A strong linear correlation was observed between the %EL volume and the %EL 3slices or the %EL 1slice in the cochlea. The Pearson correlation coefficient (r) was 0.968 (3 slices) and 0.965 (1 slice) for observer A, and 0.968 (3 slices) and 0.964 (1 slice) for observer B (P < 0.001, for all). A strong linear correlation was also observed between the %EL volume and the %EL 3slices or the %EL 1slice in the vestibule. The Pearson correlation coefficient (r) was 0.980 (3 slices) and 0.953 (1 slice) for observer A, and 0.979 (3 slices) and 0.952 (1 slice) for observer B (P < 0.001, for all). The high intra-class correlation coefficients (0.991-0.997) between the endolymph volume ratios by two observers were observed in both the cochlea and the vestibule for values of the %EL volume , the %EL 3slices and the %EL 1slice . The %EL volume might be easily estimated from the %EL 3slices or the %EL 1slice .

Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol.

PubMed

Karim, Reatul; Somani, Sukrut; Al Robaian, Majed; Mullin, Margaret; Amor, Rumelo; McConnell, Gail; Dufès, Christine

2017-01-28

The therapeutic potential of tocotrienol, a member of the vitamin E family of compounds with potent in vitro anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a novel tumor-targeted vesicular formulation of tocotrienol would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. In this work, we demonstrated that novel transferrin-bearing multilamellar vesicles entrapping α-T3 resulted in a dramatically improved (by at least 52-fold) therapeutic efficacy in vitro on A431 cell line, compared to the free drug. In addition, the intravenous administration of tocotrienol entrapped in transferrin-bearing vesicles resulted in tumor suppression for 30% of A431 and 60% of B16-F10 tumors, without visible toxicity. Mouse survival was enhanced by >13days compared to controls administered with the drug solution only. This tumor-targeted, tocotrienol-based nanomedicine therefore significantly improved the therapeutic response in cancer treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of the GLP-1 Agonist Exendin-4 on Intravenous Ethanol Self-Administration in Mice.

PubMed

Sørensen, Gunnar; Caine, S Barak; Thomsen, Morgane

2016-10-01

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to decrease ethanol (EtOH) drinking in rodent assays. The GLP-1 system also powerfully modulates food and fluid intake, gastrointestinal functions, and metabolism. To begin to understand the neurobiological mechanisms by which GLP-1 receptor ligands may be able to control EtOH intake, it is important to ascertain whether they can modulate the direct reinforcing effects of EtOH, without the confound of effects on ingestive behaviors generally. We trained experimentally naïve, free-fed C57BL/6J mice to self-administer EtOH intravenously. Once stable EtOH intake was acquired, we tested the effect of acute pretreatment with the GLP-1 receptor agonist Exendin-4. Effect of Exendin-4 on operant behavior reinforced by a palatable liquid food was similarly evaluated as a control. Intravenous EtOH functioned as a positive reinforcer in over half the mice tested. In mice that acquired self-administration, EtOH intake was high, indeed, reaching toxic doses; 3.2 μg/kg Exendin-4 decreased intravenous EtOH intake by at least 70%, but had no significant effect on food-maintained operant responding. This experiment produced 2 main conclusions. First, although technically challenging and yielding only moderate throughput, the intravenous self-administration procedure in mice is feasible, and sensitive to pharmacological manipulations. Second, GLP-1 receptor agonists can powerfully attenuate voluntary EtOH intake by directly modulating the reinforcing effects of EtOH. These findings support the potential usefulness of GLP-1 receptor ligands in the treatment of alcohol use disorder. Copyright © 2016 by the Research Society on Alcoholism.

Costs of subcutaneous and intravenous administration of trastuzumab for patients with HER2-positive breast cancer.

PubMed

Olsen, Jens; Jensen, Kenneth Forsstrøm; Olesen, Daniel Sloth; Knoop, Ann

2018-05-01

Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.) formulation. The objective of this study was to estimate the costs of administration of iv. and sc. trastuzumab treatment. Via interviews, we identified all the activities associated with iv. and sc. administration. The outcome was time estimates. To estimate the administration costs, the time estimates were valued by average gross wages.  The iv. administration takes longer time as infusion time is longer (25 or 85 min). The iv. administration is associated with higher cost for 17 cycles; €971 (€1858 vs €887). sc. administration is associated with lower administration costs. Switching patients from iv. to sc. would make it possible to treat more patients without increasing the personnel resources.

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

Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

PubMed

Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

2016-08-01

The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

Intravenous administration of stabilized antisense lipid particles (SALP) leads to activation and expansion of liver natural killer cells.

PubMed

Bramson, J L; Bodner, C A; Johnson, J; Semple, S; Hope, M J

2000-06-01

Stabilized antisense lipid particles (SALP) have been developed for the systemic delivery of oligonucleotides. The impact of intravenous SALP administration was measured with respect to activation of natural killer (NK) and NK1.1+ T (NKT) cells in the livers of immunocompetent mice. Treatment with a SALP containing a highly mitogenic oligonucleotide (INX-6295) generated an increase in NK cytolytic activity and cell number within the liver but did not appear to affect the number of hepatic NKT cells or their cytolytic activity. The same results were observed after intravenous administration of the mitogenic oligonucleotide alone. Interestingly, treatment with a SALP containing a weakly mitogenic oligonucleotide (INX-6300) also activated the liver NK cells, whereas the oligonucleotide alone was unable to elicit these effects. The NK stimulatory activity of a SALP containing INX-6300 required both lipid and oligonucleotide components. These results demonstrate that in addition to modifying the pharmacokinetics and biodistribution of intravenously administered oligonucleotides, SALP possess immunostimulatory activity independent of oligonucleotide mitogenicity, which can serve as an adjuvant to antisense therapies for cancer.

High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

PubMed

Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

2013-09-01

Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

Safety of intravenous metoprolol use in unmonitored wards: a single-centre observational study.

PubMed

Kelly, D; Hawdon, G; Reeves, J; Morris, A; Cunningham, M; Barrett, J

2015-09-01

This study aims to examine and quantify the risks associated with the use of intravenous metoprolol on unmonitored wards. This study was a retrospective single-centre observational study from 1 January 2009 to 31 December 2013. The study hospital was a 415-bed, private hospital in Melbourne, Victoria. The study population was all patients who received intravenous metoprolol on an unmonitored ward. The primary outcome measure was the rate of serious adverse events (SAE), defined as a complication of intravenous metoprolol resulting in transfer to a critical-care environment, a medical emergency team call or death. Six hundred and nine patients received a total of 8260 doses of intravenous metoprolol. Seven cases were identified with a SAE deemed possibly related to beta-blocker use and there was one death. All SAE were hypotension, giving an overall rate of hypotension of 7/609 or 1.1% (95% confidence interval (CI), 0.5 to 2.4%) with a rate per dose delivered of 0.8/1000 doses (95% CI 0.3 to 1.7). The death occurred in a 94-year-old woman with abdominal sepsis. After case file review, consensus opinion deemed this to be unrelated to intravenous metoprolol. The use of intravenous metoprolol on unmonitored wards appears to be safe. The complication rate was low, suggesting that this may be a sensible approach to the management of in-hospital populations at risk of beta-blocker withdrawal. © 2015 Royal Australasian College of Physicians.

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.

Intravenous administration of azumolene to reverse malignant hyperthermia in swine.

PubMed

do Carmo, P L; Zapata-Sudo, G; Trachez, M M; Antunes, F; Guimarães, S E F; Debom, R; Rizzi, M D R; Sudo, R T

2010-01-01

The efficacy of intravenous (IV) administration of azumolene (Az), an analogue 30-fold more soluble than dantrolene, on pigs susceptible to malignant hyperthermia (MH) is incompletely understood. To evaluate efficacy of Az on MH crisis in pigs. Eight normal (MHN) and 7 susceptible to MH (MHS) pigs (Landrace × Large White × Pietran). Prospective, laboratory trial. Hypermetabolic crisis was observed in MHS pigs, but not in MHN pigs, after a combined administration of inhaled halothane (1.5%) and IV injection of succinylcholine (SCh; 2.5 mg/kg). Susceptibility was confirmed using a caffeine and halothane contracture test. Az was administered 15 minutes after administration of SCh. Respiratory acidosis (pH 7.16 ± 0.02; Pco(2) , 46.2 ± 9.1 mmHg, HCO(3) , 22.5 ± 2.3 mmol/L), fever (38.2 ± 1.1°C), cardiac arrhythmias, and muscle contracture were observed in MHS pigs. MHS pigs (n = 5) treated with Az (2 mg/kg IV) survived the crisis with attenuation of signs (pH 7.30 ± 0.10; Pco(2) , 36.3 ± 4.5 mmHg; HCO(3) , 22.9 ± 2.3 mmol/L) and recovery of normal muscle tone and cardiac rhythm. Az represents a possible substitute for dantrolene to reverse MH crisis in susceptible pigs. Copyright © 2010 by the American College of Veterinary Internal Medicine.

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

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

PubMed

Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

2010-06-29

Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

PubMed

Meroño, Tomás; Dauteuille, Carolane; Tetzlaff, Walter; Martín, Maximiliano; Botta, Eliana; Lhomme, Marie; Saez, María Soledad; Sorroche, Patricia; Boero, Laura; Arbelbide, Jorge; Chapman, M John; Kontush, Anatol; Brites, Fernando

2017-04-01

Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p < 0.001). HDL particles from IDA patients showed higher triglyceride content (+30%,p < 0.05) and lower antioxidative capacity (-23%,p < 0.05). Although HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p < 0.05). Arylesterase activity of PON-1 was significantly lower in IDA patients than controls (-16%,p < 0.05). The intravenous administration of iron was associated with a decrease in malondialdehyde levels and an increase in arylesterase activity of PON-1 (-22% and +18%, respectively, p < 0.05). IDA is associated with oxidative stress and functionally deficient HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

PubMed

Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

2007-12-01

The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial.

PubMed

Holm, C; Thomsen, L L; Norgaard, A; Langhoff-Roos, J

2017-04-01

To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. Single-centre, open-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical fatigue score from baseline to 12 weeks postpartum. The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue and depression scores, as well as in haematological and iron parameters, all in favour of intravenous iron. There were no serious adverse reactions. A single dose of intravenous iron was associated with a statistically significant reduction in aggregated physical fatigue within 12 weeks after postpartum haemorrhage compared to standard medical care with oral iron below the prespecified criteria of clinical superiority. As patient-reported outcomes improved significantly and intravenous iron resulted in a fast hematopoietic response without serious adverse reactions, intravenous iron may be a useful alternative after postpartum haemorrhage if oral iron is not absorbed or tolerated. © 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Intravenous iron administration strategies and anemia management in hemodialysis patients.

PubMed

Michels, Wieneke M; Jaar, Bernard G; Ephraim, Patti L; Liu, Yang; Miskulin, Dana C; Tangri, Navdeep; Crews, Deidra C; Scialla, Julia J; Shafi, Tariq; Sozio, Stephen M; Bandeen-Roche, Karen; Cook, Courtney J; Meyer, Klemens B; Boulware, L Ebony

2017-01-01

The effect of maintenance intravenous (IV) iron administration on subsequent achievement of anemia management goals and mortality among patients recently initiating hemodialysis is unclear. We performed an observational cohort study, in adult incident dialysis patients starting on hemodialysis. We defined IV administration strategies over a 12-week period following a patient's initiation of hemodialysis; all those receiving IV iron at regular intervals were considered maintenance, and all others were considered non-maintenance. We used multivariable models adjusting for demographics, clinical and treatment parameters, iron dose, measures of iron stores and pro-infectious and pro-inflammatory parameters to compare these strategies. The outcomes under study were patients' (i) achievement of hemoglobin (Hb) of 10-12 g/dL, (ii) more than 25% reduction in mean weekly erythropoietin stimulating agent (ESA) dose and (iii) mortality, ascertained over a period of 4 weeks following the iron administration period. Maintenance IV iron was administered to 4511 patients and non-maintenance iron to 8458 patients. Maintenance IV iron administration was not associated with a higher likelihood of achieving an Hb between 10 and 12 g/dL {adjusted odds ratio (OR) 1.01 [95% confidence interval (CI) 0.93-1.09]} compared with non-maintenance, but was associated with a higher odds of achieving a reduced ESA dose of 25% or more [OR 1.33 (95% CI 1.18-1.49)] and lower mortality [hazard ratio (HR) 0.73 (95% CI 0.62-0.86)]. Maintenance IV iron strategies were associated with reduced ESA utilization and improved early survival but not with the achievement of Hb targets. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

PubMed

Palmer, Gene A; Brogdon, Jennifer L; Constant, Stephanie L; Tattersall, Peter

2004-02-01

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

A Nonproliferating Parvovirus Vaccine Vector Elicits Sustained, Protective Humoral Immunity following a Single Intravenous or Intranasal Inoculation

PubMed Central

Palmer, Gene A.; Brogdon, Jennifer L.; Constant, Stephanie L.; Tattersall, Peter

2004-01-01

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th1 immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4+ T cells. PMID:14722265

Intravenous administration of levothyroxine for treatment of suspected myxedema coma complicated by severe hypothermia in a dog.

PubMed

Henik, R A; Dixon, R M

2000-03-01

A 7-year-old male English Coonhound with suspected myxedema coma complicated by severe hypothermia and metabolic abnormalities was treated with a combination of active external and core rewarming techniques, i.v. and oral administration of levothyroxine, supplemental oxygen, and administration of fluids (0.9% NaCl solution). Myxedema coma develops as a consequence of severe hypothyroidism and is characterized by a hypometabolic, stuporous state. Myxedema coma is associated with a high mortality rate, and most reported cases have involved Doberman Pinschers. Intravenous administration of levothyroxine can be used successfully in combination with oral administration to restore normal metabolic function and assist in warming and thermoregulation, although dosages should be conservative to avoid adverse cardiovascular effects.

Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

2012-08-01

To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

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

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

Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

PubMed

Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

2005-05-01

To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

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

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

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

PubMed

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

2015-08-01

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. 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. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

2013-03-01

To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

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.

Meta-analysis of Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty.

PubMed

Moskal, Joseph T; Capps, Susan G

2016-09-01

Previous meta-analyses established that tranexamic acid confers benefits when used during total hip arthroplasty (THA). However, 2 of these meta-analyses included a variety of routes of administration of tranexamic acid in THA (topical, intravenous, oral, and intra-articular), another meta-analysis included a variety of antifibrinolytic drugs (not restricted to a single drug), and the final meta-analysis included nonrandomized controlled trials. This meta-analysis focused on a single medication, tranexamic acid, administered in a specific way, intravenously in patients undergoing primary THA, using data reported only in randomized controlled studies. Outcomes were restricted to blood loss, allogeneic transfusion rates, and complications. Other outcomes, such as return to function or clinical scores, could not be evaluated because of lack of consistent reporting. To better understand the effects of intravenous tranexamic acid in THA on clinical outcomes, such as recovery, return to function, and patient-reported outcome measures, it would be helpful to have more controlled trials examining these measures in a standardized manner. Intravenous tranexamic acid was beneficial for blood loss intraoperatively, blood loss through drains, and total blood loss during hospitalization, in addition to reducing allogeneic transfusion rates. No difference between intravenous tranexamic acid and placebo was found for most complications, except deep venous thrombosis, which showed favorable results with placebo. [Orthopedics.2016; 39(5):e883-e892.]. Copyright 2016, SLACK Incorporated.

A clinical and pharmacoeconomic justification for intravenous acetylcysteine: a US perspective.

PubMed

Culley, Colleen M; Krenzelok, Edward P

2005-01-01

Paracetamol (acetaminophen) poisoning remains the most common exposure reported to US poison information centres and the leading cause of poisoning-related fatalities, despite the availability of an effective antidote, acetylcysteine. Oral acetylcysteine solution has been approved for the management of acetaminophen poisoning in the US for four decades. Until the recent approval of intravenous acetylcysteine in the US, it was necessary to compound the oral solution for intravenous administration. The effectiveness and tolerability of oral and intravenous acetylcysteine for the prevention of hepatotoxicity induced by paracetamol poisoning are well established in the literature. Intravenous acetylcysteine may be preferred over oral administration based on improved tolerability, ease of administration and the shortened course of therapy (20 hours intravenous vs 72 hours oral). The two intravenous acetylcysteine regimens documented in the literature, 48 hours and 20 hours, have similar efficacy when started within 8-10 hours of ingestion. Although there are no legal concerns with continuing the routine compounding of the oral solution to an intravenous product, new standards for pharmacy compounding of sterile preparations set forth by the US Pharmacopoeia highlight that the risk of compounding products for intravenous use must be assessed carefully. Changing the route of administration of a sterile oral solution to an intravenous preparation, when a commercial sterile and pyrogen-free product is available, may not be advisable. The best cost-containment strategies must be used for introduction of the more costly sterile, pyrogen-free intravenous acetylcysteine formulation by hospitals and healthcare systems. The intravenous acetylcysteine product is more cost effective when given for 20 hours than other treatment protocols based on the costs of acetylcysteine and hospitalisation. If used per protocol, the 20-hour intravenous acetylcysteine regimen may decrease

Pharmacokinetics of mequindox and one of its major metabolites in chickens after intravenous, intramuscular and oral administration.

PubMed

Ding, Huanzhong; Liu, Yingchun; Zeng, Zhenling; Si, Hongbin; Liu, Kaiyong; Liu, Yiming; Yang, Fan; Li, Yafei; Zeng, Dongping

2012-08-01

Pharmacokinetics of mequindox and one of its major metabolites (M) was determined in chickens after intravenous (i.v.), intramuscular (i.m.) and oral administration of mequindox at a single dose of 10 (i.v. and i.m.) or 20 mg/kg b.w. (oral). Plasma concentration profiles were analyzed by a non-compartmental pharmacokinetic method. Following i.v., i.m. and oral administration, the areas under the plasma concentration-time curve (AUC(0-∞)) were 0.71±0.15, 0.67±0.21, 0.25±0.10 μg h/mL (mequindox) and 37.24±7.98, 36.40±9.16, 86.39±16.01 μg h/mL (M), respectively. The terminal elimination half-lives (t(1/2λz)) were determined to be 0.15±0.06, 0.21±0.09, 0.49±0.23 h (mequindox) and 5.36±0.86, 5.39±0.52, 5.22±0.35 h (M), respectively. The bioavailabilities (F) of mequindox were 89.4% and 16.6% for i.m. and oral administration. Steady-state distribution volume (V(ss)) of 1.20±0.34 L/kg and total body clearance (Cl(B)) of 13.57±2.16 L/kg h were determined for mequindox after i.v. dosing. After single i.m. and oral administration, peak plasma concentrations (C(max)) of 3.04±1.32, 0.36±0.13 μg/mL (mequindox) and 3.81±0.92, 5.99±1.16 μg/mL (M) were observed at t(max) of 0.08±0.02, 0.32±0.12 h (mequindox) and 0.66±0.19, 6.67±1.03 h (M), respectively. The results showed that mequindox was rapidly absorbed after i.m. or p.o. administration and most of mequindox was transformed to metabolites in chickens, with much higher C(max)s and AUCs of metabolite (M) than those of mequindox in plasma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

PubMed

Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

2009-02-01

Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

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

USDA-ARS?s Scientific Manuscript database

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...

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.

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

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

2015-12-16

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

Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection.

PubMed

Ikeda, A; Konishi, T; Ueno, M; Fukunaga, Y; Nagayama, S; Fujimoto, Y; Akiyoshi, T; Yamaguchi, T

2016-11-01

The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous

[Conversion ratio between intravenous oxycodone/hydrocotarnine and sustained-release oral oxycodone in patients with cancer pain].

PubMed

Kokubun, Hideya; Nakamura, Kazuyo; Fukawa, Misako; Matoba, Motohiro; Hoka, Sumio; Yago, Kazuo

2007-12-01

The demand for oxycodone increases in the treatment of patients with cancer pain, but there is no injection formulation containing oxycodone as a single ingredient in Japan. Instead, we have an oxycodone/hydrocotarnine compound product. Long ago, hydrocotarnine was added to enhance the analgesic effect of oxycodone. However, the mechanism of hydrocotarnine is unclear, and few studies have mentioned the conversion ratio between intravenous and oral oxycodone. In the present study, in order to define the conversion ratio between them, we investigated 18 patients treated by intravenous or oral oxycodone and changed to another administration route during their treatment. We surveyed the change in pain level and adverse effects before and after changing the administration route. The conversion ratio from oral oxycodone to intravenous oxycodone/hydrocotarnine was 0.71+/-0.12 (mean+/-S. D.), and no obvious change in adverse effect was observed.

Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

PubMed Central

Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

1996-01-01

BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811

A reliable model of intravenous MDMA self-administration in naïve mice.

PubMed

Trigo, José Manuel; Panayi, Fany; Soria, Guadalupe; Maldonado, Rafael; Robledo, Patricia

2006-01-01

MDMA is one of the most widely consumed recreational drugs in Europe. However, the mechanisms involved in the reinforcing properties of MDMA are still unclear. In this sense, the establishment of a reliable model of MDMA self-administration in mice could represent an important approach to study the neuronal substrates associated with MDMA reward by using genetically modified mice. To develop a reliable model of operant intravenous MDMA self-administration in drug-naïve mice. Mice were trained to acquire intravenous self-administration of MDMA at different doses (0, 0.06, 0.125, 0.25, 0.5 and 1.0 mg/kg/infusion) on a FR1 schedule of reinforcement for 15 consecutive days. The motivational value of different doses of MDMA (0.125, 0.25 and 0.5 mg/kg/infusion) was then tested using a progressive ratio paradigm. Finally, [3H]-mazindol autoradiographic studies were carried out in order to quantitatively assess presynaptic dopamine transporter (DAT) binding sites in the striatum of mice trained to self-administer MDMA (0 and 1.0 mg/kg/infusion) during 15 days. The latency for discrimination between the active and inactive holes, as well as the number of animals acquiring stability criteria, varied as a function of the dose of MDMA. The mice responding for intermediate doses (0.125, 0.25 and 0.5 mg/kg/infusion) discriminated earlier than those responding for low (0.06 mg/kg/infusion) or high (1.0 mg/kg/infusion) doses. The percentage of animals achieving stability criteria increased with days of testing and was inversely proportional to the dose of MDMA. The breaking points achieved for doses of 0.125 and 0.25 mg/kg/infusion were significantly higher than for a dose of 0.5 mg/kg/infusion. No significant DAT neurotoxicity was observed in the striatum of animals self-administering MDMA at a dose of 1 mg/kg/infusion. The present results show that MDMA can be reliably self-administered by drug-naïve mice.

The Assessment of Blood Loss During Total Knee Arthroplasty When Comparing Intravenous vs Intracapsular Administration of Tranexamic Acid.

PubMed

May, Jedediah H; Rieser, Geoffrey R; Williams, Chad G; Markert, Ronald J; Bauman, Ryan D; Lawless, Matthew W

2016-11-01

Administration of tranexamic acid topically and intravenously has demonstrated effectiveness in decreasing blood loss and transfusion rates. We randomized 131 patients undergoing primary total knee arthroplasty to receive either intracapsular (69) or intravenous tranexamic acid (62). Postoperative blood loss was calculated using the formula derived by Nadler et al. The number of units transfused was recorded, as well as length of hospital stay. We found no statistically significant difference on calculated blood loss (postoperative day [POD] 1: 624 ± 326 vs 644 ± 292; P = .71, POD 2: 806 ± 368 vs 835 ± 319; P = .64, and POD 3: 1076 ± 419 vs 978 ± 343; P = .55). There was no difference in number of blood transfusions, length of stay, or complications. Intracapsular tranexamic acid is not inferior to intravenous tranexamic acid in decreasing blood loss and blood transfusion rate in primary total knee arthroplasty. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of pharmacokinetics of loxoprofen and its active metabolites after an intravenous, intramuscular, and oral administration of loxoprofen in rats: evidence for extrahepatic metabolism.

PubMed

Koo, Tae-Sung; Kim, Dae-Hyun; Ahn, Sung-Hoon; Kim, Kang-Pil; Kim, In-Wha; Seo, Seung-Yong; Suh, Young-Ger; Kim, Dae-Duk; Shim, Chang-Koo; Chung, Suk-Jae

2005-10-01

The objective of this study was to characterize the extent of the formation of the active (trans-alcohol form) and inactive (cis-alcohol) metabolites of loxoprofen and to compare the kinetics after its intragastric, intravenous, and intramuscular administrations in rats. After intravenous administration of the drug at doses of 5-20 mg/kg, the clearance and the volume of distribution for loxoprofen, and the ratios of the AUC for the metabolites to the parent drug were not statistically different with the dosage; the formation clearances were 1.08 and 0.87 mL/min/kg for the active and its isomeric metabolite, respectively. After the intragastric, intravenous, or intramuscular administration, AUC for loxoprofen and the metabolites at a dose of 10 mg/kg were not statistically different for the different routes of administration. The formation of the metabolites with the concomitant loss of loxoprofen was found in incubations with liver homogenates and blood but not with a muscle homogenate or plasma, indicating that the conversion of loxoprofen to the metabolites may occur both in the liver and extraheptic tissue(s). Thus, approximately 22% of the loxoprofen may have been converted to the active metabolite in the liver and the extraheptic tissue(s) and the pharmacokinetics of the active metabolite was independent of the route of administration. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

PubMed

Loubani, Osama M; Green, Robert S

2015-06-01

The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety and Pharmacokinetics of Multiple 750-Milligram Doses of Intravenous Levofloxacin in Healthy Volunteers

PubMed Central

Chow, Andrew T.; Fowler, Cynthia; Williams, R. Rex; Morgan, Nancy; Kaminski, Susan; Natarajan, Jaya

2001-01-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation. PMID:11408234

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

PubMed

Chow, A T; Fowler, C; Williams, R R; Morgan, N; Kaminski, S; Natarajan, J

2001-07-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Pharmacokinetic behaviour of phenylglyoxal bis(guanylhydrazone) (PGBG) after intravenous administration in rabbits.

PubMed

Rodríguez, C; San Andrés, M I; San Andrés, M D; Encinas, T; González, F; Ballesteros, E

2001-04-01

Phenylglyoxal bis(guanylhydrazone) (PGBG) is a synthesized analogue of methylglyoxal bis(guanylhydrazone) (MGBG), which has demonstrated anti-parasitic activity in rabbits. The pharmacokinetic behaviour of PGBG after intravenous administration (10 mg/kg bodyweight) was studied in five rabbits. Plasma concentrations of PGBG were measured by high-performance liquid chromatography. Plasma PGBG concentrations decreased rapidly and were not detectable beyond 90 min after treatment. The mean [+/- standard deviation (SD)] volume of distribution at steady state (Vdss) was 2.19 +/- 0.47 l/kg and the mean plasma clearance value (Cl) was 29.99 +/- 3.98 ml/min kg. This drug is rapidly eliminated from the body in rabbits, having a short elimination half-life (0.93 h) and mean residence time (1.21 h).

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

PubMed Central

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

2018-01-01

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

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

2016-01-01

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.

Pharmacokinetics of imipenem after intravenous, intramuscular and subcutaneous administration to cats.

PubMed

Albarellos, Gabriela A; Denamiel, Graciela A; Montoya, Laura; Quaine, Pamela C; Lupi, Martín P; Landoni, María F

2013-06-01

The study describes the pharmacokinetics and predicted efficacy of imipenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to five adult cats at a dose of 5 mg/kg. Susceptibility to imipenem [minimum inhibitory concentration (MIC)] was determined for antimicrobial resistant Escherichia coli (n = 13) and staphylococci (n = 3) isolated from domestic cat infections (urinary system, skin and conjunctiva). Maximum plasma concentrations of imipenem were 13.45 µg/ml (IV), 6.47 µg/ml (IM) and 3.83 µg/ml (SC). Bioavailability was 93.18% (IM) and 107.90% (SC). Elimination half-lives for IV, IM and SC administration were 1.17, 1.44 and 1.55 h, respectively. All tested bacteria were susceptible to imipenem; MIC values were 0.03 µg/ml for Staphylococcus species and <0.25-0.5 µg/ml for E coli. Mean imipenem concentrations remained above a MIC of 0.5 µg/ml for approximately 4 h (IV and IM) and 9 h (SC). Imipenem would be predicted to be effective for the treatment of antimicrobial resistant bacterial infections in cats at a dosage of 5 mg/kg every 6-8 h (IV, IM), or longer for the SC route. However, clinical trials are mandatory to establish its efficacy and proper dosing.

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

Extravasation Risk Using Ultrasound-guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration.

PubMed

Rupp, Jordan D; Ferre, Robinson M; Boyd, Jeremy S; Dearing, Elizabeth; McNaughton, Candace D; Liu, Dandan; Jarrell, Kelli L; McWade, Conor M; Self, Wesley H

2016-08-01

Ultrasound-guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous (IV) contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk = 13.9, 95% confidence interval [CI] = 7.9 to 24.6). After potential confounders were adjusted for, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio = 8.6, 95% CI = 4.6 to 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. © 2016 by the Society for Academic Emergency Medicine.

Extravasation Risk Using Ultrasound Guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration

PubMed Central

Rupp, Jordan D.; Ferre, Robinson M.; Boyd, Jeremy S.; Dearing, Elizabeth; McNaughton, Candace D.; Liu, Dandan; Jarrell, Kelli L.; McWade, Conor M.; Self, Wesley H.

2016-01-01

Objective Ultrasound guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. Methods A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary-care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. Results In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk: 13.9, 95% CI: 7.7 to 24.6). After adjustment for potential confounders, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio: 8.6; 95% CI: 4.6, 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Conclusions Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. PMID:27151898

[Renal response to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages].

PubMed

Jasso-Gutiérrez, L; Araujo, B; Fuse-Moteji, R; del Castillo, E D

1976-01-01

The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.

Protein Adsorption to In-Line Filters of Intravenous Administration Sets.

PubMed

Besheer, Ahmed

2017-10-01

Ensuring compatibility of administered therapeutic proteins with intravenous administration sets is an important regulatory requirement. A low-dose recovery during administration of low protein concentrations is among the commonly observed incompatibilities, and it is mainly due to adsorption to in-line filters. To better understand this phenomenon, we studied the adsorption of 4 different therapeutic proteins (2 IgG1s, 1 IgG4, and 1 Fc fusion protein) diluted to 0.01 mg/mL in 5% glucose (B. Braun EcoFlac; B. Braun Melsungen AG, Melsungen, Germany) or 0.9% sodium chloride (NaCl; Freeflex; Fresenius Kabi, Friedberg, Germany) solutions to 8 in-line filters (5 positively charged and 3 neutral filters made of different polymers and by different suppliers). The results show certain patterns of protein adsorption, which depend to a large extent on the dilution solution and filter material, and to a much lower extent on the proteins' biophysical properties. Investigation of the filter membranes' zeta potential showed a correlation between the observed adsorption pattern in 5% glucose solution and the filter's surface charge, with higher protein adsorption for the strongly negatively charged membranes. In 0.9% NaCl solution, the surface charges are masked, leading to different adsorption patterns. These results contribute to the general understanding of the protein adsorption to IV infusion filters and allow the design of more efficient compatibility studies. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.

PubMed

Tobudic, Selma; Matzneller, Peter; Stoiser, Brigitte; Wenisch, Judith Maria; Zeitlinger, Markus; Vychytil, Andreas; Jaeger, Walter; Boehmdorfer, Michaela; Reznicek, Gottfried; Burgmann, Heinz

2012-07-01

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

Pilocarpine disposition and salivary flow responses following intravenous administration to dogs.

PubMed

Weaver, M L; Tanzer, J M; Kramer, P A

1992-08-01

Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates.

Neutropenia during High Dose Intravenous Oxacillin Therapy

PubMed Central

Ahern, Mary Jean; Hicks, Jeanne E.; Andriole, Vincent T.

1976-01-01

Five patients who developed neutropenia following intravenous administration of high dose oxacillin for serious Staphylococcus aureus infection are described. Neutropenia was reversible with cessation of intravenous oxacillin therapy. Two patients were continued on oral oxacillin without untoward effects. PMID:997595

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

PubMed

Yuan, Z F; Yin, H; Ma, W P; Xing, D L

2016-08-01

Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of

Pharmacokinetics of Intraperitoneal and Intravenous Fosfomycin in Automated Peritoneal Dialysis Patients without Peritonitis

PubMed Central

Tobudic, Selma; Matzneller, Peter; Stoiser, Brigitte; Wenisch, Judith Maria; Vychytil, Andreas; Jaeger, Walter; Boehmdorfer, Michaela; Reznicek, Gottfried; Burgmann, Heinz

2012-01-01

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose. PMID:22564843

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects.

PubMed

Scoble, Patrick J; Owens, Robert C; Puttagunta, Sailaja; Yen, Mark; Dunne, Michael W

2015-12-01

Dalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects. Ten subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo. After a single infusion of dalbavancin, the maximal plasma concentration (C max) and area under the plasma concentration-time curve (AUC) increased in a proportional manner from 500 mg to 1000 mg (C max: 157 μg/ml and 299 μg/ml; AUClast: 10,850 μg·h/ml and 22,679 μg·h/ml, on the 500-mg and 1000-mg regimens, respectively) with low inter-subject variability. The mean terminal phase half-life (t 1/2) was 204 and 193 h after the 500-mg and 1000-mg dose, respectively. Clearance and volume of distribution were similar for the two dose concentrations. Treatment-emergent adverse events reported were considered to be of mild intensity. There were no relevant changes in laboratory values or vital signs over time in subjects in either treatment group. Overall, dalbavancin 500 mg and dalbavancin 1000 mg, administered as a single 30-min infusion, was well tolerated in this population and resulted in plasma exposures similar to those in non-Asians.

Effects of intravenous, sternal, and humerus intraosseous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

PubMed

Blouin, Dawn; Gegel, Brian T; Johnson, Don; Garcia-Blanco, Jose C

2016-01-01

To determine if there were significant differences among humerus intraosseous (HIO), sternal intraosseous (SIO), and intravenous (IV) administration of 500 mL Hextend in hemodynamics or administration time in a hypovolemic swine model. Vivarium. Yorkshire swine; sample size was based on a large effect size of 0.5, an α of 0.05, and a power of 80 percent Swine were randomly assigned to one of four groups: HIO (n = 9), SIO (n = 9), IV (n = 9), and control (n = 9). Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered by either the HIO, SIO, or IV route; the control group received none. Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV among HIO, SIO, and IV groups over 8 minutes (p > 0.05). An analyses of variance determined that there was no significant difference between groups relative to time of administration (p = 0.521). When IV access is difficult, both HIO and SIO are effective techniques for rapid vascular access and the administration of Hextend for patients in hypovolemic shock.

Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

PubMed Central

Buhari, Salisu; Hashim, Kalthum; Yong Meng, Goh; Mustapha, Noordin Mohamed; Gan, Siew Hua

2012-01-01

Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID:22778699

Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.

PubMed

Fediuk, Daryl J; Wang, Tao; Chen, Yufei; Parkinson, Fiona E; Namaka, Michael P; Simons, Keith J; Burczynski, Frank J; Gu, Xiaochen

2011-10-01

The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application. Copyright © 2011 John Wiley & Sons, Ltd.

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

PubMed Central

Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

2018-01-01

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating

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. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Intraperitoneal Injection Is Not a Suitable Administration Route for Single-Walled Carbon Nanotubes in Biomedical Applications.

PubMed

Liu, Xudong; Guo, Qing; Zhang, Yuchao; Li, Jinquan; Li, Rui; Wu, Yang; Ma, Ping; Yang, Xu

2016-01-01

Given the extensive application of carbon nanotubes (CNTs) in biomedical fields, there is increasing concern regarding unintentional health impacts. Research into safe usage is therefore increasingly necessary. This study investigated the responses of the mouse brain to single-walled CNTs (SWCNTs) delivered via intraperitoneal (IP) injection and compared these results with the previous study where SWCNTs were delivered via intravenous (IV) injection so as to explore which administration route is potentially better for SWCNTs application. This study suggests SWCNTs delivered via IP injection can have negative effects on the mouse brain through oxidative stress and inflammation at high concentration exposure, but these responses were not consistent and showed no dose-dependent effect. In a previous study, the results showed that IV-delivered SWCNTs induced a more consistent and dose-dependent effect. The comparison of the 2 studies suggested that using SWCNTs at a safe dosage delivered via IV injection may be a better administration route for SWCNTs in biomedical applications.

The efficacy of intravenous ketorolac for pain relief in single-stage adjustable strabismus surgery: a prospective, randomized, placebo-controlled trial

PubMed Central

Rhiu, S; Chung, S A; Kim, W K; Chang, J H; Bae, S J; Lee, J B

2011-01-01

Purpose To determine the efficacy of preoperative intravenous ketorolac in reducing intraoperative and postoperative pain and improving patient satisfaction in patients undergoing single-stage adjustable strabismus surgery. Methods A prospective, randomized, placebo-controlled clinical trial was performed with 67 patients who underwent horizontal recti muscle surgery with adjustable sutures. The test group received intravenous ketorolac (60 mg) before surgery, and the control group received intravenous normal saline. Topical 0.5% proparacaine was administered to both groups during surgery. Vital signs including heart rate and blood pressure were recorded every 10 min throughout the surgery. The patients were asked to rate their maximum intraoperative and postoperative pain scores using a numerical pain rating scale. Patient satisfaction was also assessed using a five-point analogue scale. Results The ketorolac-premedicated patients had less pain both during and after surgery (P=0.033 and P=0.024, respectively). There were no differences in vital signs during surgery and patient satisfaction between the two groups. Conclusions Intravenous ketorolac, when administered preoperatively for single-stage adjustable strabismus surgery under topical anaesthesia, was effective in reducing pain during and after surgery. PMID:21102493

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.

Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study.

PubMed

Lightdale, J R; Hayer, C; Duer, A; Lind-White, C; Jenkins, S; Siegel, B; Elliott, G R; Heyman, M B

2001-11-01

Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration. To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms. We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a

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

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

Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

PubMed Central

Ellefsen, Kayla N; da Costa, Jose Luiz; Concheiro, Marta; Anizan, Sebastien; Barnes, Allan J; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

2015-01-01

Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC–HRMS and 2D GC–MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens’ (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4–105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. PMID:26327184

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.

PubMed

Mateos, Alonso; García-Lunar, Inés; García-Ruiz, José M; Pizarro, Gonzalo; Fernández-Jiménez, Rodrigo; Huertas, Pilar; García-Álvarez, Ana; Fernández-Friera, Leticia; Bravo, Jesús; Flores-Arias, José; Barreiro, María V; Chayán-Zas, Luisa; Corral, Ervigio; Fuster, Valentín; Sánchez-Brunete, Vicente; Ibáñez, Borja

2015-03-01

We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours. Copyright © 2014 American College of Emergency

The effect of information provision on reduction of errors in intravenous drug preparation and administration by nurses in ICU and surgical wards.

PubMed

Abbasinazari, Mohammad; Zareh-Toranposhti, Samaneh; Hassani, Abdollah; Sistanizad, Mohammad; Azizian, Homa; Panahi, Yunes

2012-01-01

Malpractice in preparation and administration of intravenous (IV) medications has been reported frequently. Inadequate knowledge of nurses has been reported as a cause of such errors. We aimed to evaluate the role of nurses' education via installation of wall posters and giving informative pamphlets in reducing the errors in preparation and administration of intravenous drugs in 2 wards (ICU and surgery) of a teaching hospital in Tehran, Iran. A trained observer stationed in 2 wards in different work shifts. He recorded the nurses' practice regarding the preparation and administration of IV drugs and scored them before and after the education process. 400 observations were evaluated. Of them, 200 were related to before education and 200 were related to after education. On a 0-10 quality scale, mean ± SD scores of before and after education were determined. Mean ± SD scores of before and after education at the 2 wards were 4.51 (± 1.24) and 6.15 (± 1.23) respectively. There was a significant difference between the scores before and after intervention in ICU (P<0.001), surgery (P<0.001), and total two wards (P<0.001). Nurses' education by using wall poster and informative pamphlets regarding the correct preparation and administration of IV drugs can reduce the number of errors.

[Toxicity studies of landiolol hydrochloride (ONO-1101) (1). Single intravenous toxicity study in rats and dogs].

PubMed

Yamaguchi, K; Kasahara, T; Yanagisawa, Y; Nanba, T; Aze, Y; Shinomiya, K; Yonezawa, H; Fujita, T

1997-12-01

Single dose toxicity studies of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, were conducted in Sprague-Dawley (SD) rats and beagle dogs. ONO-1101 was administered intravenously at a dose level of 37.5, 75, 150 or 300 mg/kg to rats of both sexes and 25, 50 or 100 mg/kg to male dogs. In the rat study, 5/6 males in the 150 mg/kg group and all animals in the 300 mg/kg group died during or right after administration. Survivors in the 150 mg/kg group showed temporal hypoactivity, bradypnea, dyspnea, tremor, loss of righting reflex and reddish lacrimation up to 5 min after injection. One male in the 150 mg/kg group had a tendency of suppression on body weight gain. No effects on clinical signs and body weight gain were seen in the 75 mg/kg group or lower. Necropsy findings showed only red tear in the majority of the decedents. In the dog study, all animals died within 6 min after administration in the 100 mg/kg group, showed ataxic gait, rolling and tachypnea followed by bradypnea and gasping/apnea. Incontinence of urine, defecation and vocalization were also seen in each one of two animals before death. Temporal hypoactivity was seen 1 min after administration in the 50 mg/kg group. No clinical signs were seen in the 25 mg/kg group. ONO-1101 did not affect bodyweight or food consumption. Necropsy findings of the decedents showed no abnormalities. It is indicated that the minimum lethal doses are 150 mg/kg in rats and 100 mg/kg in dogs.

Oral Fluid Cocaine and Benzoylecgonine Concentrations Following Controlled Intravenous Cocaine Administration

PubMed Central

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

2016-01-01

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 25 mg 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 median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h 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

Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

PubMed Central

2013-01-01

Background The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121–168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. Results No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749–6004 ng/ml) and 946 ng/ml (range: 554–1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). Conclusions The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route. PMID:23941181

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.

Stability study of docetaxel solution (0.9%, saline) using Non-PVC and PVC tubes for intravenous administration.

PubMed

Park, Kang Hoon; Chung, Dong June

2015-01-01

Di-2-ethylhexyl phthalate (DEHP) are added to poly(vinyl chloride)(PVC) infusion tubes as a plasticizer to ensure tube flexibility. In addition to previously reported disadvantages of DEHP, released DEHP molecules from PVC tubes can easily interact with surfactants in anticancer drug solutions (i.e., polysorbate 80 for Taxotere®-Inj) and reduce the solubility of docetaxel in aqueous solution during anticancer drug administration. In this study, we investigated the in vitro stability of docetaxel in a 0.9% saline solution under an intravenous administration condition using a PVC tube (high DEHP content) and non-PVC infused tube. The docetaxel solution circulating through the non-PVC tube had better solution stability than through the PVC tube(high DEHP content).

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

PubMed

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.

Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

PubMed

Puri, Basant K; Hakkarainen-Smith, Jaana S; Derham, Anne; Monro, Jean A

2015-09-01

While pharmacotherapy with intravenous ceftriaxone, a third-generation cephalosporin, is a potential treatment of Lyme neuroborreliosis, there is concern that it can cause the formation of biliary sludge, leading to hepatobiliary complications such as biliary colic, jaundice and cholelithiasis, which are reflected in changes in serum levels of bilirubin and markers of cholestatic liver injury (alkaline phosphatase and γ-glutamyltranspeptidase). It has been suggested that the naturally occurring substances α-lipoic acid and glutathione may be helpful in preventing hepatic disease. α-Lipoic acid exhibits antioxidant, anti-inflammatory and anti-apoptotic activities in the liver, while glutathione serves as a sulfhydryl buffer. The aim of this study was to determine whether co-administration of α-lipoic acid and glutathione is associated with significant changes in serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase during the treatment of Lyme neuroborreliosis with long-term intravenous ceftriaxone. Serum levels of bilirubin, alkaline phosphatase and γ-glutamyltranspeptidase were measured in 42 serologically positive Lyme neuroborreliosis patients before and after long-term treatment with intravenous ceftriaxone (2-4 g daily) with co-administration of oral/intravenous α-lipoic acid (600 mg daily) and glutathione (100 mg orally or 0.6-2.4 g intravenously daily). None of the patients developed biliary colic and there were no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels over the course of the intravenous ceftriaxone treatment (mean length 75.0 days). Co-administration of α-lipoic acid and glutathione is associated with no significant changes in serum bilirubin, alkaline phosphatase or γ-glutamyltranspeptidase levels during the treatment of neuroborreliosis with intravenous ceftriaxone.

Measurement of the fall in the level of plasma radioactivity after intravenous administration of radiohippuran as a test of renal function

PubMed Central

Briggs, J. D.; Boyle, J. A.

1965-01-01

The level of plasma radioactivity following a single intravenous injection of 131I-labelled sodium orthoiodohippurate (radiohuppuran) falls with time in a tri-exponential fashion. The rate of fall of plasma radioactivity after an intravenous injection of radiohippuran was measured over the period 25 to 40 minutes from the time of injection and was expressed as the half-life of radiohippuran. The results suggest that this procedure may provide a valid measure of renal function which is more sensitive than the blood urea estimation but less sensitive than the creatinine clearance. PMID:14304256

Effects of tibial intraosseous and intravenous administration of Hextend on time of administration and hemodynamics in a hypovolemic swine model.

PubMed

Wilson, James; Passmore, Alex; Leger, Sephra; Lannan, Johnathon; Bentley, Michael; Johnson, Don

2016-01-01

To determine if there were significant differences between the tibial intraosseous (TIO) and intravenous (IV) administration of Hextend relative to time and in hemodynamics in a hypovolemic model. Vivarium. Yorkshire swine; sample size was based on a power of 80 percent, α of 0.05, and a large effect size of 0.6. Swine were randomly assigned to one of three groups: TIO (n = 7), IV (n = 7), and control (n = 7). Swine were exsanguinated 30 percent of their blood volume. Hextend (500 mL) was administered either by the TIO or IV route; the control group received none. Time of administration of Hextend; systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and stroke volume (SV) data were collected every 2 minutes and compared by group over 8 minutes. An independent t test determined that there was no significant difference between groups relative to time of administration (p = 0.001). A repeated analysis of variance found that there were no significant differences in SBP, DBP, MAP, HR, CO, and SV between the TIO and IV groups over 8 minutes (p > 0.05) but significant differences between both TIO and IV compared to the control group (p < 0.05). TIO is an effective and easily used method to administer Hextend for patients in hypovolemic shock. Based upon the findings of this study, the TIO route might be considered the first choice for rapid vascular access and the administration of Hextend.

Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration.

PubMed

Edmondson, M A; Duran, S H; Boothe, D M; Stewart, A J; Ravis, W R

2012-08-01

Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition, was administered to six alpacas (43-71 kg) randomly assigned to two treatment groups, using an open, single-dose, two-period, randomized cross-over design at a dose of 3.4-4.4 mg/kg intravenously (i.v.) and, after a washout period, 11 mg/kg orally. Serum samples were collected and stored at -80°C until assayed by HPLC. Pharmacokinetic parameters were calculated. The mean half-lives (t(1/2)) i.v. were 0.85±0.463 and 0.520±0.256 h orally. The Cp(0) i.v. was 2467±540 ng/mL, and the C(max) was 1202±1319 ng/mL orally. T(max) occurred at 0.111±0.068 h orally. The area under the curve (AUC(0-∞)) i.v. was 895±189 and 373±217 ng*h/mL orally. The volume of distribution (V(d[area])) i.v. was 5.50±2.66 L/kg. Total body clearance (Cl) i.v. was 4.62±1.09 h; Cl/F for oral administration was 39.5±23 L/h/kg. The i.v. mean residence time (MRT) was 0.720±0.264. Oral adsorption (F) was low (5.9-19.1%) at almost three times the i.v. dosage with a large inter-subject variation. This may be due to binding with the rumen contents or enzymatic destruction. Assuming linear nonsaturable pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be needed to achieve the same i.v. serum concentration of tramadol. The t(1/2) of all three metabolites was longer than the parent drug; however, O-DMT, N-DMT, and Di-DMT metabolites were not detectable in all of the alpacas. Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research. © 2011 Blackwell Publishing Ltd.

Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers

PubMed Central

Chiesa, Joseph; Lückermann, Mark; Fischer, Carsten; Dalhoff, Axel; Fuhr, Uwe

2017-01-01

ABSTRACT Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination

A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

PubMed

Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

2015-01-01

Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures. © The Author(s) 2014.

Intravenous versus topical tranexamic acid administration in primary total knee arthroplasty: a meta-analysis.

PubMed

Shin, Young-Soo; Yoon, Jung-Ro; Lee, Hoon-Nyun; Park, Se-Hwan; Lee, Dae-Hee

2017-11-01

This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in haemoglobin levels. Studies were included in this meta-analysis to check whether they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in haemoglobin levels before and after surgery in primary TKA with TXA administered through both the IV and topical routes. Ten studies were included in this meta-analysis. The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95 % CI 0.63-2.81; n.s.) and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95 % CI 0.41 to 1.77; n.s.) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95 % CI -50.74 to 185.66 mL; n.s.), 52.1 mL greater estimated blood loss (95 % CI -155.27 to 51.03 mL; n.s.), and 51.4 mL greater total blood loss (95 % CI -208.16 to 105.31 mL; n.s.) in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in haemoglobin levels (0.02 g/dL, 95 % CI -0.36 to 0.39 g/dL; n.s.). In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in haemoglobin levels between the IV and topical administration of TXA. In addition, results from subgroup analysis evaluating the effect of the times of TXA administration through the IV route suggested that double IV dose of TXA is more effective than single dose in terms of the

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

Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits.

PubMed

Karbownik, Agnieszka; Bienert, Agnieszka; Płotek, Włodzimierz; Grabowski, Tomasz; Cerbin-Koczorowska, Magdalena; Wolc, Anna; Grześkowiak, Edmund

2017-06-01

Paracetamol is one of the most common analgesics and antipyretics applied in health care. The aim of the study was to investigate the influence of the time-of-day administration on the paracetamol pharmacokinetics and its penetration into aqueous humour (AH). Rabbits were divided into three groups: I-receiving paracetamol at 08.00 h, II-receiving paracetamol at 16.00 h, and III-receiving paracetamol at 24.00 h. Paracetamol was administered intravenously at a single dose of 35 mg/kg. The concentrations of paracetamol and its metabolite (paracetamol glucuronide) in the plasma, as well as in AH were measured with the validated HPLC-UV method. No significant differences in the pharmacokinetic parameters of paracetamol was observed. When the drug was administered at 24.00 h,  elimination half-life (t 1/2kel ) of paracetamol glucuronide was longer than when the drug was administered 08.00 h (P = 0.0193). In addition, a statistically significant increase in the paracetamol glucuronide/paracetamol ratio was observed when the drug was administered at 08.00 vs. 16.00 h (P ≤ 0.0001) and 24.00 h (P ≤ 0.0001). There was no chronobiological effect on the pharmacokinetic parameters of paracetamol.

Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

PubMed Central

2012-01-01

Backgrounds We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment. Methods Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions. Results Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia. Conclusions Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP. PMID:22443810

Mercury poisoning through intravenous administration: Two case reports with literature review.

PubMed

Lu, Qiuying; Liu, Zilong; Chen, Xiaorui

2017-11-01

Metallic mercury poisoning through intravenous injection is rare, especially for a homicide attempt. Diagnosis and treatment of the disease are challenging. A 34-year-old male presented with pyrexia, chill, fatigue, body aches, and pain of the dorsal aspect of right foot. Another case is that of a 29-year-old male who committed suicide by injecting himself metallic mercury 15 g intravenously and presented with dizzy, dyspnea, fatigue, sweatiness, and waist soreness. The patient's condition in case 1 was deteriorated after initial treatment. Imaging studies revealed multiple high-density spots throughout the body especially in the lungs. On further questioning, the patient's girlfriend acknowledged that she injected him about 40 g mercury intravenously 11 days ago. The diagnosis was then confirmed with a urinary mercury concentration of 4828 mg/L. Surgical excision, continuous blood purification, plasma exchange, alveolar lavage, and chelation were performed successively in case 1. Blood irrigation and chelation therapy were performed in case 2. The laboratory test results and organ function of the patient in case 1 gradually returned to normal. However, in case 2, the patient's dyspnea was getting worse and he finally died due to toxic encephalopathy and respiratory failure. Early diagnosis and appropriate treatment are critical for intravenous mercury poisoning. It should be concerned about the combined use of chelation agents and other treatments, such as surgical excision, hemodialysis and plasma exchange in clinical settings.

Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes

PubMed Central

Selker, Harry P.; Beshansky, Joni R.; Sheehan, Patricia R.; Massaro, Joseph M.; Griffith, John L.; D’Agostino, Ralph B.; Ruthazer, Robin; Atkins, James M.; Sayah, Assaad J.; Levy, Michael K.; Richards, Michael E.; Aufderheide, Tom P.; Braude, Darren A.; Pirrallo, Ronald G.; Doyle, Delanor D.; Frascone, Ralph J.; Kosiak, Donald J.; Leaming, James M.; Van Gelder, Carin M.; Walter, Gert-Paul; Wayne, Marvin A.; Woolard, Robert H.; Opie, Lionel H.; Rackley, Charles E.; Udelson, James E.

2014-01-01

Context Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration. Objective To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS). Design, Setting, and Participants Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. Intervention Intravenous GIK solution (n=411) or identical-appearing 5% glucose placebo (n=460) administered by paramedics in the out-of-hospital setting and continued for 12 hours. Main Outcome Measures The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation. Results There was no significant difference in the rate of progression to MI among patients who received GIK (n=200; 48.7%) vs those who received placebo (n=242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66–1.13; P=.28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40–1.29; P=.27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27–0.85; P=.01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR

Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses.

PubMed

Grimsrud, K N; Mama, K R; Thomasy, S M; Stanley, S D

2009-04-01

Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry. Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve. These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.

Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial.

PubMed

Sörgel, Fritz; Thyroff-Friesinger, Ursula; Vetter, Andrea; Vens-Cappell, Bernhard; Kinzig, Martina

2009-05-22

HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations. An open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation. The haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5-101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCtau ratio and 90% confidence interval: 89.2% [82.5-96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected. HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be

[Main pharmacokinetic parameters of p-tyrosol after intravenous injection in rats. Part III: Distribution of p-tyrosol in rat].

PubMed

Chernyshova, G A; Plotnikov, M B; Smol'iakova, V I; Krasnov, E A

2011-01-01

Distribution of p-tyrosol in organism was studied in rats after a single intravenous administration in a dose of 200 mg/kg. It was shown that p-tyrosol rapidly penetrates into well perfused organs (brain, heart, kidneys). The maximum concentration ofp-tyrosol in these organs was determined in 1 minute after administration, and the mean distribution constant was within 0.8-1.11. The albumin bound fraction ofp-tyrozol amounted to 0.26-0.30.

Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

PubMed Central

2011-01-01

Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti

Perioperative intravenous fluid prescribing: a multi-centre audit.

PubMed

Harris, Benjamin; Schopflin, Christian; Khaghani, Clare; Edwards, Mark

2015-01-01

Excessive or inadequate intravenous fluid given in the perioperative period can affect outcomes. A number of guidelines exist but these can conflict with the entrenched practice, evidence base and prescriber knowledge. We conducted a multi-centre audit of intraoperative and postoperative intravenous fluid therapy to investigate fluid administration practice and frequency of postoperative electrolyte disturbances. A retrospective audit was done in five hospitals of adult patients undergoing elective major abdominal, gastrointestinal tract or orthopaedic surgery. The type, volume and quantity of fluid and electrolytes administered during surgery and in 3 days postoperatively was calculated, and electrolyte disturbances were studied using clinical records. Data from four hundred thirty-one patients in five hospitals covering 1157 intravenous fluid days were collected. Balanced crystalloid solutions were almost universally used in the operating theatre and were also the most common fluid administered postoperatively, followed by hypotonic dextrose-saline solutions and 0.9 % sodium chloride. For three common uncomplicated elective operations, the volume of fluid administered intraoperatively demonstrated considerable variability. Over half of the patients received no postoperative fluid on day 1, and even more were commenced on free oral fluids immediately postoperatively or on day 1. Postoperative quantities of sodium exceeded the recommended amounts for maintenance in half of the patients who continued to receive intravenous fluids. Potassium administration in those receiving intravenous fluids was almost universally inadequate. Hypokalaemia and hyponatraemia were the common findings. We documented the current clinical practice and confirmed that early free oral fluids and cessation of any intravenous fluids is common postoperatively in keeping with the aims of enhanced recovery after surgery programmes. Excessive sodium and water and inadequate potassium in those

Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

PubMed Central

Gonçalves de Albuquerque, Cassiano Felippe; Burth, Patrícia; Younes Ibrahim, Mauricio; Garcia, Diogo Gomes; Bozza, Patrícia Torres; Castro Faria Neto, Hugo Caire; Castro Faria, Mauro Velho

2012-01-01

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets. PMID:22529526

Reduced plasma nonesterified fatty acid levels and the advent of an acute lung injury in mice after intravenous or enteral oleic acid administration.

PubMed

Gonçalves de Albuquerque, Cassiano Felippe; Burth, Patrícia; Younes Ibrahim, Mauricio; Garcia, Diogo Gomes; Bozza, Patrícia Torres; Castro Faria Neto, Hugo Caire; Castro Faria, Mauro Velho

2012-01-01

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

PubMed

Fernández-Varón, Emilio; Cárceles-García, Carlos; Serrano-Rodríguez, Juan Manuel; Cárceles-Rodríguez, Carlos M

2016-10-13

Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica

Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration

PubMed Central

Benincosa, Lisa; Birnböck, Herbert; Boswell, C Andrew; Bumbaca, Daniela; Cowan, Kyra J; Danilenko, Dimitry M; Daugherty, Ann L; Fielder, Paul J; Grimm, Hans Peter; Joshi, Amita; Justies, Nicole; Kolaitis, Gerry; Lewin-Koh, Nicholas; Li, Jing; McVay, Sami; O'Mahony, Jennifer; Otteneder, Michael; Pantze, Michael; Putnam, Wendy S; Qiu, Zhihua J; Ruppel, Jane; Singer, Thomas; Stauch, Oliver; Theil, Frank-Peter; Visich, Jennifer; Yang, Jihong; Ying, Yong

2012-01-01

Subcutaneous (SC) delivery is a common route of administration for therapeutic monoclonal antibodies (mAbs) with pharmacokinetic (PK)/pharmacodynamic (PD) properties requiring long-term or frequent drug administration. An ideal in vivo preclinical model for predicting human PK following SC administration may be one in which the skin and overall physiological characteristics are similar to that of humans. In this study, the PK properties of a series of therapeutic mAbs following intravenous (IV) and SC administration in Göttingen minipigs were compared with data obtained previously from humans. The present studies demonstrated: (1) minipig is predictive of human linear clearance; (2) the SC bioavailabilities in minipigs are weakly correlated with those in human; (3) minipig mAb SC absorption rates are generally higher than those in human and (4) the SC bioavailability appears to correlate with systemic clearance in minipigs. Given the important role of the neonatal Fc-receptor (FcRn) in the PK of mAbs, the in vitro binding affinities of these IgGs against porcine, human and cynomolgus monkey FcRn were tested. The result showed comparable FcRn binding affinities across species. Further, mAbs with higher isoelectric point tended to have faster systemic clearance and lower SC bioavailability in both minipig and human. Taken together, these data lend increased support for the use of the minipig as an alternative predictive model for human IV and SC PK of mAbs. PMID:22453096

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

PubMed

Berthet, Carole; Castillo, Ximena; Magistretti, Pierre J; Hirt, Lorenz

2012-01-01

Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

PubMed

Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Langhoff-Roos, Jens

2015-01-14

Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin

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

USDA-ARS?s Scientific Manuscript database

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...

Successful management of ivermectin-induced blindness in an African lion (Panthera leo) by intravenous administration of a lipid emulsion.

PubMed

Saqib, Muhammad; Abbas, Ghazanfar; Mughal, Mudassar Niaz

2015-11-26

Ivermectin is widely used in veterinary practice for the treatment of ecto- and endo-parasites. In wildlife, an extra-label use this parasiticide is sometimes associated with toxicity. Different treatment regimens have been used in ivermectin toxicosis. The present report describes a successful reversal of ivermectin toxicity by intravenous administration of a commercially available lipid emulsion in a captive African lion (Panthera leo). A 2-year old captive African lion (Panthera leo) weighing ~130 kg was presented with acute neurological impairment and bilateral blindness that had developed 24 h after ivermectin exposure. The animal was treated with a commercially available lipid emulsion along with supportive therapy and experienced complete recovery. To our knowledge, this is the first case report of the use of lipid emulsion in the management of ivermectin induced blindness in an African lion and it appears that intravenous lipid emulsion may be an effective therapy in ivermectin toxicity in lions. Further testing in expanded clinical trials is clearly warranted.

[Peripheral intravenous catheter-related phlebitis].

PubMed

van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

2011-01-01

Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

PubMed

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis.

PubMed

Lin, Chunmei; Qi, Yingmei; Jie, Li; Li, Hong-Biao; Zhao, Xi-Cheng; Qin, Lei; Jiang, Xin-Qiang; Zhang, Zhen-Hua; Ma, Liping

2016-12-01

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the efficacy and safety of combined topical with intravenous tranexamic acid (TXA) versus topical, intravenous TXA alone or control for reducing blood loss after a total knee arthroplasty (TKA). In May 2016, a systematic computer-based search was conducted in the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Wanfang database. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. Only patients prepared for primary TKA that administration combined topical with intravenous TXA with topical TXA, intravenous (IV) TXA, or control group for reducing blood loss were included. Eligible criteria were published RCTs about combined topical with intravenous TXA with topical alone or intravenous alone. The primary endpoint was the total blood loss and need for transfusion. The complications of deep venous thrombosis (DVT) were also compiled to assess the safety of combined topical TXA with intravenous TXA. Relative risks (RRs) with 95% CIs were estimated for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. The Cochrane risk of bias tool was used to appraise a risk of bias. Stata 12.0 software was used for meta-analysis. Fifteen studies involving 1495 patients met the inclusion criteria. The pooled meta-analysis indicated that combined topical TXA with intravenous TXA can reduce the total blood loss compared with placebo with a mean of 458.66 mL and the difference is statistically significant (MD = -458.66, 95% CI: -655.40 to 261.91, P < 0.001). Compared with intravenous TXA, combined administrated TXA can decrease the total blood loss, and the difference is statistically significant (MD = -554.03, 95% CI: -1066.21 to -41.85, P = 0.034). Compared with the topical administration TXA, the

Efficacy of combined intravenous immunoglobulins and steroids in children with primary immune thrombocytopenia and persistent bleeding symptoms.

PubMed

Parodi, Emilia; Giordano, Paola; Rivetti, Elisa; Giraudo, Maria Teresa; Ansaldi, Giulia; Davitto, Mirella; Mondino, Anna; Farruggia, Piero; Amendola, Giovanni; Matarese, Sofia M R; Rossi, Francesca; Russo, Giovanna; Ramenghi, Ugo

2014-07-01

The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1-3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. A response (i.e. platelet count >50×10(9)/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings.

Effect of Intravenous Administration of Contrast Media on Serum Creatinine Levels in Neonates.

PubMed

Bedoya, Maria A; White, Ammie M; Edgar, J Christopher; Pradhan, Madhura; Raab, Elisabeth L; Meyer, James S

2017-08-01

Purpose To assess the effect of intravenous contrast media on renal function in neonates. Materials and Methods Institutional review board approval was obtained with waiver of consent. Electronic health records from January 2011 to April 2013 were reviewed retrospectively. Measures of renal function were obtained in inpatient neonates who underwent magnetic resonance (MR) imaging or computed tomography (CT) and for whom serum creatinine (Cr) levels were obtained within 72 hours before imaging and at least one time after imaging (>1 day after administration of contrast material). A total of 140 neonates who received contrast material (59 who underwent CT with iohexol or iodixanol and 81 who underwent MR imaging with gadopentetate dimeglumine) were identified. These neonates were frequency matched according to sex, gestational and postnatal age, and preimaging serum Cr levels with neonates who underwent unenhanced MR imaging or CT. Cr levels and glomerular filtration rates (GFRs) were grouped according to when they were obtained (before imaging, 1-2 days after imaging, 3-5 days after imaging, 6-9 days after imaging, 10-45 days after imaging, and more than 45 days after imaging). Serum Cr levels and GFRs for each time period were compared between groups by using hierarchic regressions or χ 2 or Fisher exact tests and with repeated-measures analysis of variance to compare groups on the rate of change in serum Cr levels and GFRs from before to after imaging. Results Cr levels decreased and GFRs increased in both groups from before to after imaging (CT group, P ≤ .01; MR imaging group, P ≤ .01). The neonates who underwent contrast material-enhanced imaging and the neonates who underwent unenhanced imaging showed similar serum Cr levels at all examined time periods. Groups also did not differ in the proportion of neonates with serum Cr levels higher than the reference range (>0.4 mg/dL) at any time point (iodine- [P > .12] or gadolinium-based [P > .13] contrast

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

PubMed

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2014-11-01

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

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

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial.

PubMed

von Au, Alexandra; Milloth, Eva; Diel, Ingo; Stefanovic, Stefan; Hennigs, Andre; Wallwiener, Markus; Heil, Joerg; Golatta, Michael; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Schuetz, Florian; Domschke, Christoph

2016-01-01

Patients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness. In this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter. Between 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts. We conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pediatric procedural sedation with ketamine: time to discharge after intramuscular versus intravenous administration.

PubMed

Ramaswamy, Preeti; Babl, Franz E; Deasy, Conor; Sharwood, Lisa N

2009-02-01

Ketamine is an attractive agent for pediatric procedural sedation. There are limited data on time to discharge comparing intramuscular (IM) vs. intravenous (IV) ketamine. The authors set out to determine whether IM or IV ketamine leads to quicker discharge from the emergency department (ED) and how side effect profiles compare. All patients who had received ketamine IM or IV at a tertiary children's hospital ED during the 3-year study period (2004-2007) were identified. Prospective sedation registry data, retrospective medical records, and administrative data were reviewed for drug dosages, use of additional agents, time of drug administration to discharge, total ED time (triage to discharge), and adverse events. A subgroup analysis for patients requiring five or fewer sutures (short suture group) was performed. A total of 229 patients were enrolled (60% male) with median age of 2.8 years (IQR =1.8-4.3 years) and median weight of 15.7 kg (range = 8.7-74 kg). Ketamine was most frequently employed for laceration repair (80%) and foreign body removal (9%). Overall, 48% received ketamine IM and 52% received it IV. In the short-suture subgroup, 52% received ketamine IM, while 48% received it IV. Multivariate linear regression analysis determined time from drug administration to patient discharge as 21 minutes shorter for IV compared with IM administration, adjusted for age and number of additional doses (R(2) = -0.35; 95% CI = -0.5 to -0.19; p < 0.001). Total time in the ED (triage to discharge) comparing IV versus IM administration, adjusting for age and gender and number of additional doses, was not significantly different (p = 0.16). In the short-suture subgroup, time to discharge from administration was also shorter in the IV ketamine group (R(2) = -0.454; 95%CI = -0.66 to -0.25; p < 0.001) but similar for total time in ED (p = 0.16). Overall, adverse events occurred in 35% (95% CI = 27% to 45%) of the IM group and 20% (95% CI = 13% to 28%) of the IV group (p = 0

Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

PubMed

Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

2011-04-01

Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

Studies on target tissue distribution of ginsenosides and epimedium flavonoids in rats after intravenous administration of Jiweiling freeze-dried powder.

PubMed

Liu, Minyan; Wang, Hongtao; Zhao, Shaohua; Shi, Xiaowei; Zhang, Yongfeng; Xu, Honghui; Wang, Yufeng; Li, Xiangjun; Zhang, Lantong

2011-11-01

A simple and rapid liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for analysis of ginsenoside Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, icariin and epimedin A, B, C in rat target tissues (spinal cord, brain, muscle and sciatic nerve) after intravenous administration of Jiweiling freeze-dried powder using genistein as an internal standard (IS). The tissue samples were treated by protein precipitation with methanol prior to HPLC and chromatographic separation was performed on a C18 column utilizing a gradient elution program with acetonitrile and 0.1% formic acid aqueous. Electrospray ionization (ESI) source was employed and the 11 analytes and IS were detected by multiple reaction monitoring (MRM) scanning under the negative ionization mode. Higher sensitivity was achieved and the optimized mass transition ion-pairs (m/z) for quantitation were selected. The calibration curves were linear over the investigated concentration ranges with correlation coefficients higher than 0.995. The intra- and inter-day RSDs were all less than 10% with the relative error (RE) within ± 9.3%. The mean extraction recoveries for all compounds were between 93.3 and 106%. The proposed method was successfully applied to investigate the target tissue distribution of the 11 compounds in rat after intravenous administration of Jiweiling freeze-dried powder. Copyright © 2011 John Wiley & Sons, Ltd.

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

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

PubMed

Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

2007-08-01

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was <10 microg/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5 microg/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

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.

Does Intravenous Midazolam Dose Influence the Duration of Recovery Room Stay Following Outpatient Third Molar Surgery?

PubMed

Ettinger, Kyle S; Jacob, Adam K; Viozzi, Christopher F; Van Ess, James M; Fillmore, W Jonathan; Arce, Kevin

2015-12-01

To evaluate the impact of intravenous midazolam dose on the duration of recovery room stay for patients undergoing outpatient third molar surgery. Using a retrospective cohort study design, a sample of patients undergoing outpatient third molar surgery under intravenous sedation at Mayo Clinic from 2010 to 2014 was identified. All patients underwent extraction of all 4 third molars during a single operative procedure and the age range was limited to 14 to 29 years. The primary predictor variable was the total dose of intravenous midazolam administered during sedation. The primary outcome variable was recovery room length of stay (LOS) after completion of surgery. Multiple covariates also abstracted included patient age, gender, American Society of Anesthesiologists (ASA) score, duration of surgical procedure, complexity of surgical procedure, types and dosages of all intravenous medications administered during sedation, and volume of crystalloid fluid administered perioperatively. Univariable and multivariable models were developed to evaluate associations between the primary predictor variable and covariates relative to the primary outcome variable. The study sample was composed of 2,610 patients. Mean age was 18.3 years (SD, 3.0 yr; range, 14 to 29 yr) and gender distribution was 52% female. Mean dosage of midazolam administered was 4.1 mg (SD, 1.1 mg; range, 0.5 to 10.0 mg). Variables predicting shorter LOS at multivariable analysis included older age (P < .001), male gender (P = .004), and administration of larger crystalloid fluid volumes (P < .001). Variables predicting longer LOS included higher ASA score (P < .001), administration of ketamine (P < .001), and administration of ketorolac (P < .001). The dose of midazolam administered during sedation was not found to be significantly associated with prolonged recovery room LOS in univariable or multivariable settings. Dosage of intravenous midazolam does not appear to significantly impact the

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

PubMed

Sumbria, Rachita K; Zhou, Qing-Hui; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Boado, Ruben J; Pardridge, William M

2013-04-01

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

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

USDA-ARS?s Scientific Manuscript database

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...

Primary Intravenous Set Consumption Across 3 Branded Infusion Pumps

PubMed Central

Hedlund, Nancy; Sarangpur, Shishir; Kayler, Shannon; O'Brien, Kathy

2017-01-01

This retrospective study of 6426 hip replacement, coronary artery bypass graft, and colectomy surgeries across 23 US hospitals found that intravenous (IV) set designs that can be interchanged for use both in gravity-fed and automated pump delivery systems are replaced less frequently than IV sets designed for use primarily by one delivery method. Semistructured interviews with nurses highlighted the impact of set design on nursing workflow when moving between gravity-fed and pump-based administration. Use of interchangeable, single-design IV sets across gravity and automated infusions minimizes disruptions to closed systems, may reduce nurses being distracted from patients' clinical needs when replacing sets, and may yield supply cost savings. PMID:28682999

Metabolic disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and skin administration in rats.

PubMed

Fediuk, Daryl J; Wang, Tao; Chen, Yufei; Parkinson, Fiona E; Namaka, Michael P; Simons, Keith J; Burczynski, Frank J; Gu, Xiaochen

2012-01-01

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.

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. Copyright 2016, SLACK Incorporated.

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

PubMed

Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

2016-11-01

To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

[Therapeutic administration of immunoglobulins].

PubMed

Witte, T

2016-12-01

Intravenously administered immunoglobulins have multiple modes of action that are anti-inflammatory. They can therefore be beneficial in a number of autoimmune disorders. The aim of this article is to analyze and summarize studies on the administration of intravenous immunoglobulins in rheumatological diseases. A selective search and analysis of the literature was carried out related to the mode of action and efficacy of intravenous immunoglobulins in rheumatological diseases. Intravenous immunoglobulins have a broad mode of action and can therefore be beneficial in almost all autoimmune diseases. Conditions in which they are of special benefit include immunothrombopenia (ITP), Kawasaki disease and idiopathic inflammatory myopathies. In rare situations, they may also be indicated in systemic lupus erythematosus (SLE), Sjögren's syndrome and neuropathies, catastrophic antiphospholipid syndrome (APS), scleroderma, antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, pyoderma gangrenosum and scleromyxedema. Severe adverse events are rare. In view of the high costs of the therapy, intravenous immunoglobulins are mostly applied in emergency situations, as salvage therapy when other standard therapies have failed or when severe infections are a contraindication to the administration of immunosuppressants.

Efficacy of combined intravenous immunoglobulins and steroids in children with primary immune thrombocytopenia and persistent bleeding symptoms

PubMed Central

Parodi, Emilia; Giordano, Paola; Rivetti, Elisa; Giraudo, Maria Teresa; Ansaldi, Giulia; Davitto, Mirella; Mondino, Anna; Farruggia, Piero; Amendola, Giovanni; Matarese, Sofia M.R.; Rossi, Francesca; Russo, Giovanna; Ramenghi, Ugo

2014-01-01

Background The aim of this study was to investigate the effect of the combined administration of intravenous immunoglobulins and steroids as a second-line therapy in 34 children with primary immune thrombocytopenia and persistent, symptomatic bleeding. Materials and methods Combined therapy (intravenous immunoglobulins 0.4 g/kg daily on days 1 and 2, and methylprednisolone 20 mg/kg daily on days 1–3) was administered to 12 patients with newly diagnosed ITP who did not respond to the administration of a single therapy (either intravenous immunoglobulins or steroids) and to 22 children with persistent and chronic disease who required frequent administrations (i.e. more frequently than every 30 days) of either immunoglobulins or steroids (at the same standard dosages) in order to control active bleeding. Results A response (i.e. platelet count >50×109/L and remission of active bleeding) was observed in 8/12 (67%) patients with newly diagnosed ITP. The clinical presentation of responders and non-responders did not differ apparently. Patients in the chronic/persistent phase of disease had a significantly longer median period of remission from symptoms compared with the previous longest period of remission (p=0.016). The treatment was well tolerated. Discussion Our data suggest that the combined approach described is a well-tolerated therapeutic option for children with primary immune thrombocytopenia and persistent bleeding symptoms that can be used in both emergency and/or maintenance settings. PMID:24887226

45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2014-10-01 2014-10-01 false Capacity of treatment for intravenous substance...

45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2013-10-01 2013-10-01 false Capacity of treatment for intravenous substance...

45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2012-10-01 2012-10-01 false Capacity of treatment for intravenous substance...

45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2011-10-01 2011-10-01 false Capacity of treatment for intravenous substance...

45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2010-10-01 2010-10-01 false Capacity of treatment for intravenous substance...

Smart syringe pumps for drug infusion during dental intravenous sedation

PubMed Central

Lee, Kiyoung

2016-01-01

Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump. PMID:28884149

Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines.

PubMed

Ravis, W R; Comerci, C; Ganjam, V K

1986-01-01

Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.

Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

PubMed

Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

2015-11-01

Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand

Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report was to determine the pharmacokinetic properties, safety, and tolerability of single and multiple doses of intravenous delafloxacin. In addition, the absolute bioavailability (BA) of the 450-mg tablet formulation of delafloxacin was determined. Three clinical trials are summarized. The first study was a randomized, double-blind, placebo-controlled, single- (300, 450, 600, 750, 900, and 1200 mg) ascending-dose study of IV delafloxacin in 62 (52 active, 10 placebo) healthy volunteers. The second study was a randomized, double-blind, placebo-controlled study of IV delafloxacin (300 mg) given as a single dose on day 1, followed by twice-daily dosing on days 2 through 14; 12 (8 active, 4 placebo) healthy volunteers were enrolled. The third study was an open-label, randomized, 2-period, 2-sequence crossover study in which 56 healthy volunteers were randomly assigned to 1 of 2 sequences of a single oral dose of delafloxacin (450-mg tablet) or IV delafloxacin (300 mg). Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were calculated. Delafloxacin Cmax values increased proportionally with increasing single IV dose for the dose range of 300 to 1200 mg, whereas the AUC values increased more than proportionally to dose for the same dose range. The mean terminal half-life of delafloxacin was approximately 12 hours (ranging from 8 to 17 hours). The volume of distribution (Vd) at steady state was approximately 35 L, which is similar to the volume of total body water. There was minimal accumulation of delafloxacin after twice-daily IV administration of 300 mg with an accumulation ratio of 1.09. The delafloxacin total exposure after a single 1-hour IV infusion of 300 mg and a single oral dose of a 450-mg tablet were equivalent with geometric least square mean ratio (90% CI) of 0.8768 (0.8356-0.9200) for AUC0-∞ and 0.8445 (0.8090-0.8815) for AUC0-t, respectively. The Cmax values of delafloxacin were not

Use of intravenous immunoglobulin in pediatric practice

PubMed Central

Zülfikar, Bülent; Koç, Başak

2014-01-01

In recent years, human-driven intravenous immunoglobulins (IVIG) administered intravenously have been widely used in treatment of many diseases. Intravenous immunoglobulin is obtained from human-driven plasma pools as in other plasma-driven products and IVIG preperations contain structurally and functionally intact immunoglobulin. Intravenous immunoglobulin was approved by FDA (Food and Drug Administration) in USA in 1981 for the first time and was started to be primarily used in patients with immune deficiency with hypogammaglobulinemia. The effects of intravenous immunoglobulin include complex mechanisms, but it exerts its essential action by eliminating the non-specific Fc receptors found in the mononuclear phagocytic system or by inhibiting binding of immune complexes to Fc receptors in the cells. Their areas of usage include conditions where their anti-inflammatory and immunomudulator effects are utilized in addition to replacement of deficient immunoglobulin. Although the definite indications are limited, it has been shown that it is useful in many diseases in clinical practice. Its side effects include fever, sweating, nausea, tachycardia, eczematous reactions, aseptic meningitis, renal failure and hematological-thromboembolic events. In this article, use of IVIG, its mechanisms of action, indications and side effects were discussed. PMID:26078679

[Efficacy of intravenous phenobarbital treatment for status epilepticus].

PubMed

Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

2013-08-01

Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

A noticeable phenomenon: thiol terminal PEG enhances the immunogenicity of PEGylated emulsions injected intravenously or subcutaneously into rats.

PubMed

Wang, Chunling; Cheng, Xiaobo; Sui, Yue; Luo, Xiang; Jiang, Gongping; Wang, Yu; Huang, Zhenjun; She, Zhennan; Deng, Yihui

2013-11-01

Repeated intravenous injection of long-circulating methoxy-polyethylene glycol (PEG)-liposomes alters the pharmacokinetics and biodistribution of the second administration, regarded as the "accelerated blood clearance (ABC) phenomenon." Nevertheless, the effect of terminal groups of distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) on the induction of the ABC phenomenon had not been reported previously. In this study, rats were injected intravenously or subcutaneously with PEG coated emulsions (DE) which were prepared using PEG terminated with either the methoxyl (OCH3), hydroxyl (OH), amino (NH2), carboxyl (COOH), or thiol (SH) group. DE-OCH3 demonstrated the longest prolonged half-life in vivo after a single intravenous injection, followed by DE-SH and DE-COOH. In contrast, DE-OH was rapidly removed from the blood circulation, as was DE-NH2. Moreover, we observed a strong positive relationship between the circulation time of initially injected PEGylated emulsions and the extent to which the ABC phenomenon was induced, but a exception of DE-SH increasing the ABC effect. Furthermore, the present study suggested that thiols might stimulate the proliferation and differentiation of B cells to induce the fastest clearance of the second intravenous administration by inducing the synthesis of the cell membrane and cytosolic proteins or reacting with follicular dendritic cells. The results strongly suggested that thiol groups played a stimulatory role in the immune response and provided a considerable implication for multiple drug therapy of thiol groups. Copyright © 2013 Elsevier B.V. All rights reserved.

Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Fiorelli, Alfonso; Mazzella, Antonio; Passavanti, Beatrice; Sansone, Pasquale; Chiodini, Paolo; Iannotti, Mario; Aurilio, Caterina; Santini, Mario; Pace, Maria Caterina

2015-09-01

To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P = 0.01), C-reactive protein (P < 0.001) and morphine consumption (P < 0.001). No acute psychological side effects related to the use of ketamine were registered. The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

PubMed

DeNoble, Victor J; Mele, Paul C

2006-03-01

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

PubMed

Zdarova Karasova, Jana; Zemek, Filip; Kunes, Martin; Kvetina, Jaroslav; Chladek, Jaroslav; Jun, Daniel; Bures, Jan; Tachecí, Ilja; Kuca, Kamil

2013-01-01

Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration. Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight. The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment. I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

PubMed

Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

1990-01-01

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Effect of rate of delivery of intravenous cocaine on self-administration in rats.

PubMed

Schindler, Charles W; Panlilio, Leigh V; Thorndike, Eric B

2009-10-01

Many studies of drug self-administration in primates have shown that faster infusions of a drug are more reinforcing than slower infusions. Similar effects have not been shown in rats. We assessed the influence of delivery rate by allowing rats to choose between the same doses of intravenous cocaine delivered over two different infusion speeds. Rats were trained in chambers containing two nose-poke response devices. In Experiment 1, responses in one nose-poke delivered 0.3 mg/kg/injection of cocaine over 10 s, and responses in the other delivered the same dose over 100 s. In Experiment 2, the same procedure was used, but with 1.0 mg/kg/injection dose delivered over 1.7 versus 100 s. During acquisition, most rats preferred the faster infusion. When the delivery rates associated with the nose pokes were reversed, rats trained with 0.3 mg/kg/injection failed to switch nose-poke preference, but half the rats trained with 1.0 mg/kg/injection did switch. In Experiment 3, the choice was between 1 mg/kg cocaine delivered over 1.7 s and no reinforcement. Here, rats quickly learned to respond in the nose-poke associated with cocaine and quickly switched their choice during reversal. In Experiment 4, two groups of rats were allowed to choose between food delivered with a delay of 1 versus 5 s or 1 versus 10 s, respectively. Rats preferred the shorter delay during initial training. In reversal, some rats in the 1 vs 5 s group failed to reverse, while all the rats in the 1 vs 10 s group reversed. These results show that faster infusions of cocaine are clearly more reinforcing during acquisition, but delivery rate may not be as important to the maintenance of self-administration once it has been established. The results with food suggest that these findings represent general principles of behavior and are not unique to drug self-administration.

Sex differences in nicotine intravenous self-administration: A meta-analytic review.

PubMed

Flores, Rodolfo J; Uribe, Kevin P; Swalve, Natashia; O'Dell, Laura E

2017-11-21

This report reflects a meta-analysis that systematically reviewed the literature on intravenous self-administration (IVSA) of nicotine in female and male rats. The goal was to determine if sex differences in nicotine IVSA exist, estimate the magnitude of the effect, and identify potential moderators of the relationship between sex differences and nicotine consumption. Extensive search procedures identified 20 studies that met the inclusion criteria of employing both female and male rats in nicotine IVSA procedures. The meta-analysis was conducted on effect size values that were calculated from mean total intake or nicotine deliveries using the Hedges' unbiased g u statistic. A random effects analysis revealed that overall females self-administered more nicotine than males (weighted g u =0.18, 95% CI [0.003, 0.34]). Subsequent moderator variable analyses revealed that certain procedural conditions influenced the magnitude of sex differences in nicotine IVSA. Specifically, higher reinforcement requirements (>FR1) and extended-access sessions (23h) were associated with greater nicotine IVSA in females versus males. Females also displayed higher nicotine intake than males when the experiment included a light cue that signaled nicotine delivery. Sex differences were not influenced by the diurnal phase of testing, dose of nicotine, or prior operant training. Overall, the results revealed that female rats display higher levels of nicotine IVSA than males, suggesting that the strong reinforcing effects of nicotine promote tobacco use in women. Copyright © 2017 Elsevier Inc. All rights reserved.

Administration of intravenous morphine for acute pain in the emergency department inflicts an economic burden in Europe

PubMed Central

Casamayor, Montserrat; Hennebert, Marc; Brazzi, Luca; Prosen, Gregor

2018-01-01

Background Acute pain is among the leading causes of referral to the emergency department (ED) in industrialized countries. Its management mainly depends on intensity. Moderate-to-severe pain is treated with intravenous (IV) administered opioids, of which morphine is the most commonly used in the ED. We have estimated the burden of IV administration of morphine in the five key European countries (EU5) using a micro-costing approach. Scope A structured literature review was conducted to identify clinical guidelines for acute pain management in EU5 and clinical studies conducted in the ED setting. The data identified in this literature review constituted the source for all model input parameters, which were clustered as analgesic (morphine), material used for IV morphine administration, nurse workforce time and management of morphine-related adverse events and IV-related complications. Findings The cost per patient of IV morphine administration in the ED ranges between €18.31 in Spain and €28.38 in Germany. If costs associated with the management of morphine-related adverse events and IV-related complications are also considered, the total costs amount to €121.13–€132.43. The main driver of those total costs is the management of IV-related complications (phlebitis, extravasation and IV prescription errors; 73% of all costs) followed by workforce time (14%). Conclusions IV morphine provides effective pain relief in the ED, but the costs associated with the IV administration inflict an economic burden on the respective national health services in EU5. An equally rapid-onset and efficacious analgesic that does not require IV administration could reduce this burden. PMID:29675049

Effects of Rapid Intravenous Rehydration in Children With Mild-to-Moderate Dehydration.

PubMed

Janet, Sophie; Molina, Juan Carlos; Marañón, Rafael; García-Ros, Marta

2015-08-01

New guidelines for "rapid or ultrarapid" intravenous rehydration are being developed in different emergency departments. These new guidelines propose a faster administration of fluids and electrolytes than in traditional protocols. However, there is still insufficient evidence to establish a standard protocol. Our objective was to determine the effects of an outpatient rapid intravenous rehydration regimen based on the administration of 0.9% saline + 2.5% dextrose, at a rate of 20 mL/kg per hour for 2 hours, in children with mild-to-moderate isonatremic dehydration resulting from acute gastroenteritis. We performed a 2-institution, prospective, observational, descriptive study. Eighty-three patients were included in the study. All patients underwent a first evaluation, including physical examination, laboratory tests, and assessment of clinical degree of dehydration. After this initial evaluation, all children received our intravenous rehydration regimen. A second evaluation including the same items as in the first one was made after in all the children. Intravenous rehydration was successful in 69 patients (83.1%). It failed in 14 patients (16.8%), who required hospitalization because of persistent vomiting in 9 patients and poor general appearance in 5 patients. After intravenous rehydration, we observed a statistically significant decrease in the levels of ketonemia and uremia and in the Gorelick scale score. However, no significant changes were observed in sodium, chloride, potassium, and osmolarity values. We conclude that, in children with mild-to-moderate dehydration, the administration of 20 mL/kg per hour for 2 hours of 0.9% saline solution + 2.5% glucose improved clinical scores and may be used as an alternative and safe way for intravenous rehydration.

Viewing videotaped identification procedure increases juror sensitivity to single-blind photo-array administration.

PubMed

Modjadidi, Karima; Kovera, Margaret Bull

2018-06-01

We investigated whether watching a videotaped photo array administration or expert testimony could sensitize jurors to the suggestiveness of single-blind eyewitness identification procedures. Mock jurors recruited from the community (N = 231) watched a videotaped simulation of a robbery trial in which the primary evidence against the defendant was an eyewitness identification. We varied whether the witness made an identification from a single- or double-blind photo array, the evidence included a videotape of the photo array procedure, and an expert testified about the effects of single-blind identification procedures on administrators' behaviors and witness accuracy. Watching the videotaped photo array administration sensitized mock jurors to the suggestiveness of the single-blind procedure, causing them to be less likely to convict a defendant identified through single-rather than double-blind procedures. Exposure to the videotaped procedure also decreased the favorability of mock jurors' ratings of the eyewitness, irrespective of whether the lineup was conducted by a single-blind administrator. Expert testimony did not sensitize jurors to administrator bias. Thus, videotaping identification procedures could serve as an important procedural reform that both preserves a record of whether the lineup administration was suggestive and might improve jurors' evaluations of eyewitness evidence. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Comparison of the efficacy of intravenous tranexamic acid with and without topical administration versus placebo in urgent endoscopy rate for acute gastrointestinal bleeding: A double-blind randomized controlled trial

PubMed Central

Tavakoli, Nader; Agah, Shahram; Azizi, Ali; Masoodi, Mohsen; Amiri, Hassan; Sheikhvatan, Mehrdad; Syedsalehi, Bahare; Behnam, Behdad; Arabahmadi, Mehran; Mehrazi, Maryam

2017-01-01

Background Tranexamic acid (TXA), a synthetic antifibrinolytic drug, is effective as a treatment for serious hemorrhage, including bleeding arising from major trauma and post-operative interventions. Significant acute gastrointestinal bleeding may have a poor outcome despite routine medical and endoscopic treatments. The aim of this study was to assess whether early intravenous and/or intravenous plus topical administration of TXA reduces the need for urgent endoscopy for acute gastrointestinal bleeding. Method This double-blind randomized clinical trial included 410 patients with proven acute gastrointestinal bleeding. All patients received conventional therapy. The subjects were randomized to three groups: (A) 138 patients received intravenous TXA (1 g q6h); (B) 133 patients received topical TXA (1 g single dose by nasogastric tube) plus systemic TXA; and (C) 139 patients received a placebo (sodium chloride 0.9%) for 24 hours. Subgroup statistical analyses were conducted for urgent endoscopy, mortality, re-bleeding, blood transfusion, endoscopic and/or surgical intervention rates, and health status. Results The time to endoscopy was significantly shorter in group C (15.58 ± 7.994, p < 0.001). A need for urgent endoscopy was seen in 14.49%, 10.52%, and 30.21% of patients in groups A, B, and C, respectively (p < 0.001). No significant statistical differences were seen between treatment groups regarding mortality, re-bleeding, blood transfusion, and endoscopic and/or surgical intervention rates. No thromboembolic event was documented during the 1-week follow up. Conclusions Our results showed that the antifibrinolytic properties of TXA can aid in changing an urgent endoscopy to an elective procedure, with better outcomes for both physicians and patients. PMID:29435313

Oral and Intravenous Fumonisin Exposure in Pigs—A Single-Dose Treatment Experiment Evaluating Toxicokinetics and Detoxification

PubMed Central

Schertz, Hanna; Kluess, Jeannette; Frahm, Jana; Schatzmayr, Dian; Dohnal, Ilse; Bichl, Gerlinde; Schwartz-Zimmermann, Heidi; Breves, Gerhard; Dänicke, Sven

2018-01-01

We examined the toxicokinetics of fumonisin B1 (FB1) and its main metabolites after single dose application intravenously (iv) of 139 nmol FB1 or hydrolyzed FB1 (HFB1)/kg bodyweight (BW) in barrows (BW: 34.4 kg ± 2.7 kg), as well as the toxicokinetics of FB1, FB2, FB3 and FB1 bioavailability from oral exposure (3425 nmol FB1/kg BW, on top of ration). Additionally, detoxification efficacy of FumD (240 U/kg feed; 3321 nmol FB1/kg BW), a fumonisin esterase, was examined for oral fumonisin application. Urine and feces were collected quantitatively and serum samples were taken over a period of 120 h. Serum toxicokinetics of FB1iv showed a short distribution half-life of 6 min followed by a longer elimination half-life of 36 min. After HFB1iv administration, serum clearance was three times higher compared to FB1iv group (5.6 and 1.8 L/kg/h respectively) which together with a 5-times higher volume of distribution indicates that HFB1 is more rapidly cleared from systemic circulation but distributed more extensively into the extravasal space than FB1. The bioavailability of FB1 in orally exposed pigs was 5.2% (incl. metabolites). Moreover, we found a significant reduction of FB1 bioavailability by 90% caused by the action of fumonisin esterase in the gastrointestinal tract, clearly demonstrating the efficacy of FumD. PMID:29621161

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Phlebitis as a consequence of peripheral intravenous administration of cisatracurium besylate in critically ill patients.

PubMed

Meeder, Annelijn M; van der Steen, Marijke S; Rozendaal, Annemieke; van Zanten, Arthur R H

2016-10-03

This case report series describes 3 cases of cisatracurium besylate associated phlebitis after an infusion period of 14-20 hours. No similar cases have been reported in the literature. Association of phlebitis with another neuromuscular blocking agent, atracurium, has been described in the literature. The acidity of atracurium is thought to be the main cause. It is recommended that atracurium is administered only via central venous catheters when indicated to infuse over prolonged periods of time due to the acidity. Cisatracurium is a stereoisomer of atracurium and as such has the same molecular weight. Although cisatracurium also has a similar acidity as atracurium, a recommendation concerning infusion via a central venous catheter is lacking. We suggest prolonged administration of cisatracurium besylate only via centrally placed venous catheters or if not possible to careful monitor relevant peripheral intravenous sites to diminish the risks of phlebitis and associated complications or other cutaneous reactions. 2016 BMJ Publishing Group Ltd.

Population Pharmacokinetics of Combined Intravenous and Local Intrathecal Administration of Meropenem in Aneurysm Patients with Suspected Intracranial Infections After Craniotomy.

PubMed

Li, Xingang; Sun, Shusen; Wang, Qiang; Zhao, Zhigang

2018-02-01

For patients with intracranial infection, local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid (CSF). However, a large inter-individual variability may pose treatment efficacy at risk. This study aimed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method. After craniotomy, aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled. Venous blood and CSF specimens were collected for determining meropenem concentrations. Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model. The proposed model was applied to simulate dosage regimens. A three-compartmental model was established to describe meropenem in vivo behavior. Lumbar CSF drainage resulted in a drug loss, and drug clearance in CSF (CL CSF ) was employed to describe this. The covariate analysis found that the drainage volume (mL/day) was strongly associated with CL CSF , and the effect of creatinine clearance was significant on the clearance of meropenem in blood (CL). Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations. Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume. This model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing.

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

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

PubMed

Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

2017-02-01

1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

Optimizing the use of intravenous therapy in internal medicine.

PubMed

Champion, Karine; Mouly, Stéphane; Lloret-Linares, Celia; Lopes, Amanda; Vicaut, Eric; Bergmann, Jean-François

2013-10-01

We aimed to evaluate the impact of physicians' educational programs in the reduction of inappropriate intravenous lines in internal medicine. Fifty-six French internal medicine units were enrolled in a nationwide, prospective, blinded, randomized controlled trial. Forms describing the patients with an intravenous line and internal medicine department characteristics were filled out on 2 separate days in January and April 2007. Following the first visit, all units were randomly assigned to either a specific education program on the appropriate indications of an intravenous line, during February and March 2007, or no training (control group). The Investigators' Committee then blindly evaluated the clinical relevance of the intravenous line according to pre-established criteria. The primary outcome was the percentage of inappropriate intravenous lines. During January 2007, intravenous lines were used in 475 (24.9%) of the 1910 hospitalized patients. Of these, 80 (16.8%) were considered inappropriate. In April 2007, 416 (22.8%) of the 1823 hospitalized patients received an intravenous line, which was considered in 10.2% (21/205) of patients managed by trained physicians, versus 16.6% (35/211) of patients in the control group (relative difference 39%; 95% confidence interval, -0.6-13.3; P = .05). Reduced intravenous administration of fluids, antibiotics, and analgesics accounted for the observed decrease. The use of a simple education program reduced the rate of inappropriate intravenous lines by almost 40% in an internal medicine setting (NCT01633307). Copyright © 2013 Elsevier Inc. All rights reserved.

Intravenous maintenance fluid therapy in children.

PubMed

McNab, Sarah

2016-02-01

Intravenous fluids are frequently used in paediatrics but have been associated with significant adverse outcomes. Understanding the composition of fluid prescribed and administering an appropriate rate is essential for safe fluid administration, along with regular monitoring. Recent evidence has shown that using an isotonic fluid with a sodium concentration similar to plasma can decrease the risk of hyponatraemia without an increase in adverse effects. This should lead to a change in guidelines: isotonic fluid should now be used as the primary maintenance intravenous fluid given to the majority of children. © 2016 The Author Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.

2010-01-01

The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potentmore » decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.« less

Time course for measuring endolymphatic size in healthy volunteers following intravenous administration of gadoteridol.

PubMed

Naganawa, Shinji; Suzuki, Kojiro; Yamazaki, Masahiro; Sakurai, Yasuo; Ikeda, Mitsuru

2014-01-01

We developed semi-quantitative methods to measure endolymphatic size on images obtained 4 hours after intravenous administration of single-dose gadolinium-based contrast medium (IV-SD-GBCM) and found little variation in results between observers. We used the methods to measure the size of the endolymph in healthy volunteers at various times after IV-SD-GBCM and attempted to determine the optimal timing for the evaluation. In 8 healthy male volunteers, we obtained heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) images 1.5, 3, 4.5, and 6 hours after IV-SD-GBCM as positive perilymph images (PPI) as well as acquiring positive endolymph images (PEI) and magnetic resonance cisternography (MRC). To evaluate the endolymph, we generated 2 kinds of processed images (HYDROPS-Mi2 and HYDROPS2-Mi2) by subtracting PEI or MRC from PPI as previously proposed. We semi-quantitatively measured the ratio of the area of the endolymph (%EL) to that of total lymph on the 2 kinds of generated images for the cochlea and vestibule according to the previously proposed method. We analyzed statistics to evaluate the change in %EL over time and used analysis of variance (ANOVA) for a 2 × 4 repeated-measures design to assess difference in image type. We adopted 5% as a significance level. The %EL was significantly larger at 1.5 hours after IV-SD-GBCM than at 3, 4.5, and 6 hours in both the cochlea and vestibule for both kinds of generated images. Between 4.5 and 6 hours, the %EL plateaued for both the cochlea and vestibule, and the 2 kinds of generated images did not differ significantly. A delay of 1.5 hours after IV-SD-GBCM is not sufficient to evaluate endolymphatic size. The %EL plateaus between 4.5 and 6 hours. These data might be valuable for further clinical studies.

[Anaphylaxis needing adrenaline administration during anesthesia: a 7-year single-institution study].

PubMed

Kayashima, Kenji; Sozen, Reiko

2013-10-01

Adrenaline is the key treatment for acute anaphylaxis; however, it is difficult to use it appropriately in terms of dosage and timing. If used incorrectly, adrenaline can cause cardiac infarction, stroke, recurrence and other problems. We collected data of suspected anaphylaxis from records in our anesthesia department between April 2005 and March 2012. All cases where the skin of patients turned red and blood pressure decreased continuously were included. We analyzed the usage of adrenaline in these cases. Six (0.034%) suspected anaphylaxis cases were analyzed from a total of 27,597 anesthesia cases. Adrenaline was administered subcutaneously in 2 cases, intravenously in 3 cases, and with and infused in 1 case. In the 4 cases with intravenous administration, the median dose was 0.52 (range : 0.02-1.6) mg. Following decreased and unstable blood pressure, adrenaline was initiated after a median of 12.5 (5-25) min, and blood pressure returned to normal after 20 (5-95) min. Patients were extubated 19 (4-24) hours after observation of anomalous blood pressure. No aftereffects or recurrences were observed. Adrenaline was administered appropriately in terms of dosage, but timing should have been earlies in 3 of 6 cases.

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

PubMed

Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

Low-dose intravenous lidocaine as treatment for proctalgia fugax.

PubMed

Peleg, Roni; Shvartzman, Pesach

2002-01-01

Proctalgia fugax is characterized by a sudden internal anal sphincter and anorectic ring attack of pain of a short duration. Description of the influence of intravenous lidocaine treatment for proctalgia fugax. A 28-year-old patient suffering of proctalgia fugax for 8 months. Conventional treatment efforts did not improve his condition. A single dose of an intravenous lidocaine infusion completely stopped his pain attacks. Based on the experience reported in this case and the potential benefit of this treatment for proctalgia fugax, controlled studies comparing intravenous lidocaine with placebo should be conducted to confirm the observation and to provide a more concrete basis for the use of intravenous lidocaine for this indication.

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

PubMed

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.

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

Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

PubMed

van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

2015-10-01

This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 μmol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This

Intravenous Levetiracetam in the Rat Pilocarpine-Induced Status Epilepticus Model: Behavioral, Physiological and Histological Studies

PubMed Central

Zheng, Yi; Moussally, Jon; Cash, Sydney S.; Karnam, Havisha B.; Cole, Andrew J.

2010-01-01

Purpose Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality. Intravenous levetiracetam (LEV), an antiepileptic drug approved to treat partial seizures, has recently been introduced. We sought to determine the effect of LEV administered intravenously in a chemoconvulsant model of status epilepticus. Methods We examined the effect of intravenous LEV in the rat lithium-pilocarpine model of status epilepticus. Ten or 30 minutes after the onset of behavioral status epilepticus, animals were treated with LEV (200–1200 mg/kg i.v.) administered in a single bolus. Behavioral responses were recorded. Selected animals had continuous EEG recording before, during and after the administration of LEV. Some animals were sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury. Results When administered 30 minutes after the onset of behavioral epileptic seizures, transient attenuation of ictal behavior was observed in animals treated with 800 mg/kg or more of LEV. The duration of behavioral attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from a mean of 4 minutes to 23.6 minutes. When administered 10 minutes after seizure onset, 400 mg/kg of LEV resulted in transient ictal behavioral attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine also delayed the onset of seizures. EEG recordings, however, showed no significant attenuation of ictal discharge. By contrast, TUNEL staining demonstrated less neuronal injury in hippocampii and other limbic structures in animals that responded behaviorally to LEV. Conclusions Intravenous administration of LEV in a chemoconvulsant model of status epilepticus results in attenuation of behavioral manifestations of seizure discharge and in reduction of neuronal injury but does not significantly alter ictal discharge recorded by EEG

Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: behavioral, physiological and histological studies.

PubMed

Zheng, Yi; Moussally, Jon; Cash, Sydney S; Karnam, Havisha B; Cole, Andrew J

2010-01-01

Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality. Intravenous levetiracetam (LEV), an anti-epileptic drug approved to treat partial seizures, has recently been introduced. We sought to determine the effect of LEV administered intravenously in a chemoconvulsant model of status epilepticus. We examined the effect of intravenous LEV in the rat lithium-pilocarpine model of status epilepticus. Ten or 30 min after the onset of behavioral status epilepticus, animals were treated with LEV (200-1200 mg/kg i.v.) administered in a single bolus. Behavioral responses were recorded. Selected animals had continuous EEG recording before, during and after the administration of LEV. Some animals were sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury. When administered 30 min after the onset of behavioral epileptic seizures, transient attenuation of ictal behavior was observed in animals treated with 800 mg/kg or more of LEV. The duration of behavioral attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from a mean of 4-23.6 min. When administered 10 min after seizure onset, 400 mg/kg of LEV resulted in transient ictal behavioral attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine also delayed the onset of seizures. EEG recordings, however, showed no significant attenuation of ictal discharge. By contrast, TUNEL staining demonstrated less neuronal injury in hippocampii and other limbic structures in animals that responded behaviorally to LEV. Intravenous administration of LEV in a chemoconvulsant model of status epilepticus results in attenuation of behavioral manifestations of seizure discharge and in reduction of neuronal injury but does not significantly alter ictal discharge recorded by EEG. Copyright 2009 Elsevier Ltd. All rights reserved.

Oral triazolam pretreatment for intravenous sedation.

PubMed Central

Stopperich, P. S.; Moore, P. A.; Finder, R. L.; McGirl, B. E.; Weyant, R. J.

1993-01-01

This double-blind, controlled clinical trial assessed the anxiety relief provided by oral triazolam given before intravenous sedation. Twenty-two healthy adults undergoing third-molar surgery with intravenous sedation were enrolled in this study. Subjects were randomly assigned to receive either 0.25 mg of triazolam p.o. or an identically appearing placebo 45 to 60 min before venipuncture. Immediately before test drug administration, subjects completed the Corah Anxiety Scale, a Visual Analog Scale (VAS) assessing state anxiety, and the Interval Scale of Anxiety Response (ISAR). The VAS and ISAR were repeated immediately before venipuncture. Intravenous sedation medications consisted of fentanyl, midazolam, and methohexital. At 24 hr, assessments of the venipuncture and global experience were obtained. Results indicated that the characteristics of the triazolam and placebo patients were similar at baseline. With triazolam pretreatment, both the VAS and ISAR scores decreased significantly. Dose requirements for conscious sedation medications were decreased in the triazolam group. Patients rated the venipuncture experience significantly less unpleasant when pretreated with triazolam, and global ratings of the overall surgical experience favored triazolam. An oral-intravenous combination sedation technique using 0.25 mg of triazolam may have a significant therapeutic advantage for outpatient oral surgery. PMID:7943920

Intravenous fluids for reducing the duration of labour in low risk nulliparous women.

PubMed

Dawood, Feroza; Dowswell, Therese; Quenby, Siobhan

2013-06-18

hyponatraemia (serum sodium levels < 135 mmol/L ). For neonatal complications, there was no difference in the admission to NICU) or in low Apgar scores, however 33.3% of babies developed hyponatraemia in the dextrose group compared to 13.3 % in the normal saline group (RR 0.40, 95% CI 0.17 to 0.93) (P = 0.03). One trial reported a higher incidence of neonatal hyperbilirubinaemia in the dextrose group of babies. There was no difference in neonatal hypoglycaemic episodes between groups. Although the administration of intravenous fluids compared with oral intake alone demonstrated a reduction in the duration of labour, this finding emerged from only two trials. The findings of other trials suggest that if a policy of no oral intake is applied, then the duration of labour in nulliparous women may be shortened by the administration of intravenous fluids at a rate of 250 mL/hour rather than 125 mL/hour. However, it may be possible for women to simply increase their oral intake rather than being attached to a drip and we have to consider whether it is justifiable to persist with a policy of 'nil by mouth'. One trial raised concerns about the safety of dextrose and this needs further exploration.None of the trials reported on the evaluation of maternal views of being attached to a drip during their entire labour. Furthermore, there was no objective assessment of dehydration. The evidence from this review does not provide robust evidence to recommend routine administration of intravenous fluids. Interpreting the results from trials was hampered by the low number of trials contributing data and by variation between trials. In trials where oral fluids were not restricted there was considerable variation in the amount of oral fluid consumed by women in different arms of the same trial, and between different trials. In addition, results from trials were not consistent and risk of bias varied. Some important research questions were addressed by single trials only, and important outcomes

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

Melorheostosis and its treatment with intravenous zoledronic acid

PubMed Central

Hollick, Rosemary Jane; Black, Alison; Reid, David

2010-01-01

We report a case of melorheostosis, a rare bone disorder characterised by mesodermal dysplasia, and its successful and prolonged treatment with the intravenous bisphosphonate zoledronic acid. The middle-aged man presented with pain and swelling of his tibia, which was diagnosed by imaging and bone biopsy as being due to melorheostosis. There was early symptom control after a single infusion of intravenous zoledronic acid. Prolonged symptom relief was accompanied by long-term suppression of the bone resorption marker β cross-laps. We suggest that melorheostosis can be treated with intravenous zoledronic acid and that treatment can be monitored by the use of a specific bone resorption marker. PMID:22479293

EFFECT OF SINGLE AND REPEATED TETRACYCLINE ADMINISTRATION ON THE PHAGOCYTIC FUNCTION OF RETICULENDOTHELIAL SYSTEMS

DTIC Science & Technology

It was previously established that single administration of chlortetracycline and oxytetracycline to white mice stimulates the absorptive function of...upon repeated administration. The effect of single and repeated administration of chlortetracycline, tetracycline, and oxytetracycline on the absorptive function of mouse RES were studied.

An overview of intravenous-related medication administration errors as reported to MEDMARX, a national medication error-reporting program.

PubMed

Hicks, Rodney W; Becker, Shawn C

2006-01-01

Medication errors can be harmful, especially if they involve the intravenous (IV) route of administration. A mixed-methodology study using a 5-year review of 73,769 IV-related medication errors from a national medication error reporting program indicates that between 3% and 5% of these errors were harmful. The leading type of error was omission, and the leading cause of error involved clinician performance deficit. Using content analysis, three themes-product shortage, calculation errors, and tubing interconnectivity-emerge and appear to predispose patients to harm. Nurses often participate in IV therapy, and these findings have implications for practice and patient safety. Voluntary medication error-reporting programs afford an opportunity to improve patient care and to further understanding about the nature of IV-related medication errors.

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

PubMed

Harel, Ziv; Kamel, Kamel S

2016-01-01

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. 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. 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. 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 given as a continuous intravenous infusion over 60 minutes in patients with severe

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

The use of solid lipid nanoparticles to target a lipophilic molecule to the liver after intravenous administration to mice.

PubMed

Lu, Wen; He, Lang Chong; Wang, Chang He; Li, Yan Hua; Zhang, San Qi

2008-10-01

Taspine solid lipid nanoparticles (Ta-SLN) and taspine solid lipid nanoparticles modified by galactoside (Ta-G2SLN) were prepared by the film evaporation-extrusion method. The nanoparticles were spherical or near-spherical particles with smooth surface, small size and high encapsulation efficiency. Ta-G2SLN and Ta-SLN showed significant inhibition on 7721 cell growth. Intravenous injection of either Ta-SLN or Ta-G2SLN resulted in a higher plasma and liver concentration and a longer retention time in mice compared with the administration of Ta. These results suggested that SLN tended to be preferentially delivered to the liver and Ta-G2SLN may further enhance liver targeting.

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

PubMed

Hokkanen, Ann-Helena; Raekallio, Marja R; Salla, Kati; Hänninen, Laura; Viitasaari, Elina; Norring, Marianna; Raussi, Satu; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

2014-07-01

To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Randomised, prospective clinical study. Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Detomidine at 80 μg kg(-1) was administered to ten calves sublingually (GEL) and at 30 μg kg(-1) to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg(-1) ) and local anaesthetic (lidocaine 3 mg kg(-1) ) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student's t-test and linear mixed models as relevant. The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL(-1) (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Oromucosally administered detomidine is an effective sedative agent for calves prior to disbudding. © 2014 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

PM101: intravenous amiodarone formulation changes can improve medication safety.

PubMed

Souney, Paul F; Cooper, Warren D; Cushing, Daniel J

2010-03-01

Intravenous amiodarone (A-IV) is used to manage ventricular and atrial arrhythmias. The current formulation uses polysorbate 80 and benzyl alcohol to maintain amiodarone in solution, and these co-solvents are linked with clinically-important adverse events and pharmaceutical incompatibilities. PM101 is a recently FDA-approved intravenous formulation of amiodarone that uses a cyclodextrin to solubilize amiodarone. This review describes the clinical and pharmaceutical development of formulations of amiodarone for intravenous administration. The medical and pharmaceutical literature was searched for papers discussing A-IV, PM101 and their formulation components. Relevant literature was identified starting from 1948 to the present. The reader will learn about the important medical and pharmaceutical issues complicating A-IV administration, including an understanding of related hypotension and compatibility with commonly used infusion materials and how these issues may impact drug safety. PM101 has been developed to address several of these important issues. PM101 is a new formulation of A-IV that is stable in commonly used infusion materials and avoids co-solvent related toxicities.

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (1). Single-dose intravenous toxicity studies in rats and dogs].

PubMed

Yanagi, H; Yamaguchi, K; Shimizu, K; Shichino, Y; Nishiyama, K; Mori, H; Shinomiya, K; Ueda, H; Suzuki, Y; Yonezawa, H; Fujita, T

1998-07-01

Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO-5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity, bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and above. In particular, one of six female rats in the 450 mg/kg group showed clonic convulsion and died. In surviving animals, those signs disappeared within 3 hr after administration. No effect on body weight gain was seen in either group. Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the right knee joint muscle, tendon and lung in a dead animal. In the dog study, no effects on clinical signs, body weight, food consumption and blood biochemistry were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.

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.

Randomized controlled trial of intravenous acetaminophen for postcesarean delivery pain control.

PubMed

Altenau, Brie; Crisp, Catrina C; Devaiah, C Ganga; Lambers, Donna S

2017-09-01

Cesarean delivery is a common surgery in the United States, with 1.3 million performed during 2009. 1 Obstetricians must balance the growing concern with opioid abuse, dependence, and side effects with optimal postoperative pain control. Intravenous acetaminophen may represent an additional method to decrease the reliance on opioid medications and improve postoperative pain following cesarean delivery. The objective of the study was to determine whether the administration of intravenous acetaminophen following routine scheduled cesarean delivery would decrease the need for narcotic medications to control postoperative pain. This was an institutional review board-approved, double-blind, placebo-controlled, randomized trial, registered on clinicaltrials.gov (number 02046382). Women scheduled to undergo cesarean delivery with regional anesthesia at term were recruited. All perioperative and postpartum care was standardized via study order sets. Study patients were given all medications in a standardized manner receiving either acetaminophen 1000 mg intravenously or 100 mL saline (placebo) every 8 hours for 48 hours for a total of 6 doses. The pharmacy prepared intravenous acetaminophen and saline in identical administration bags labeled study drug to ensure blinding. The initial dose of study drug was given within 60 minutes of skin incision. Quantity of breakthrough and scheduled analgesic medications and self-reported pain levels on the Faces Pain Scale (0-10) before and after study drug administration were collected. Patient demographics were extracted from the chart. Power calculation determined that 45 patients per arm were required to detect a 30% reduction in postcesarean narcotic requirement with 80% power and a significance level of P = .05. A total of 133 patients were consented for the study. Twenty-nine were excluded and 104 patients completed the study: 57 received intravenous acetaminophen and 47 received placebo. There were no differences in baseline

Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and ∆ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs

PubMed Central

Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W.; Schlote, Julia; Ewald, Andreas H.; Menger, Michael D.; Maurer, Hans H.; Schmidt, Peter H.

2017-01-01

Background: Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4) as well as ∆9-tetrahydrocannabinol (THC) as reference were examined in pigs. Methods: Pigs (n = 6 per drug) received a single intravenous 200 µg/kg BW dose of JWH-210, RCS-4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. Results: The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination. Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. PMID:27834143

Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and Δ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs.

PubMed

Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Ewald, Andreas H; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

2017-01-01

Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1- pentyl-indol-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) as reference were examined in pigs. Pigs (n = 6 per drug) received a single intravenous 200 μg/kg BW dose of JWH-210, RCS- 4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.

PubMed

Griffenhagen, Gregg M; Rezende, Marlis L; Gustafson, Daniel L; Hansen, Ryan J; Lunghofer, Paul J; Mama, Khursheed R

2015-09-01

To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. Prospective experimental study. Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05). Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1)  minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats. © 2014 Association of Veterinary Anaesthetists and the

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

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. © 2012 Blackwell Publishing Ltd.

Postoperative administration of landiolol hydrochloride for patients with supraventricular arrhythmia: the efficacy of sustained intravenous infusion at a low dose.

PubMed

Wariishi, Seiichiro; Yamashita, Koichi; Nishimori, Hideaki; Fukutomi, Takashi; Yamamoto, Masaki; Radhakrishnan, Geethalakshmi; Sasaguri, Shiro

2009-11-01

The purpose of this study was to investigate the efficacy of landiolol hydrochloride, a short-acting beta(1) blocker, by initiating its administration at a low dose (5 microg kg(-1) min(-1)) in patients with postoperative supraventricular arrhythmia. The efficacy of landiolol was evaluated in 38 patients who, after developing postoperative atrial flutter or fibrillation, with sinus tachycardia and two patients who had a history of paroxysmal atrial fibrillation with frequent atrial extrasystole. The heart rate and blood pressure before and 2 h after the administration of landiolol were compared. A return to the sinus rhythm from supraventricular arrhythmia was noted in 89%. The heart rate was reduced from 137+/-26 bpm (before landiolol administration) to 93+/-18 bpm (2 h after the start of the medication, P<0.01). As an agent to correct an arrhythmic condition, landiolol successfully raised the systolic blood pressure from 108+/-24 mmHg (before medication) to 120+/-19 mmHg (2 h after the medication was started, P<0.05). Continuous intravenous infusion of landiolol at a low dose was found to be effective for postoperative supraventricular arrhythmia.

Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers.

PubMed

Hatorp, V; Oliver, S; Su, C A

1998-12-01

Repaglinide is a novel prandial glucose regulator (PGR) for the treatment of type 2 diabetes. In order to investigate subject variability following oral administration of repaglinide, and to determine the relative and absolute bioavailabilities of repaglinide following oral or intravenous administration, two single-centre, open-label, randomized, crossover clinical studies were conducted. Study 1 was conducted in 24 healthy male subjects (aged 18 to 49 years), who received repaglinide 2 mg, as either tablet or oral solution, twice each on 4 separate occasions at least 7 days apart. Study 2 was conducted in 12 healthy male subjects (aged 18 to 45 years), who received repaglinide 2 mg, either as a tablet or as an intravenous infusion over 15 minutes, once each on 2 separate occasions, with a washout period of 7-10 days. In study 1 there was no significant difference between administration of repaglinide 2 mg, in either tablet or oral solution form with regard to intrasubject variation in AUC and Cmax. However, the intrasubject variation in t(max) and mean residence time (MRT) was significantly (p = 0.001) larger for the tablets than for the oral solution. Intersubject variation (CV) in AUC ranged from 44.7% to 62.1% after oral administration. The relative bioavailability of repaglinide (AUC(tablet)/AUC(oral solution)) was 110% (95% CI, 103%-117%). In study 2 the absolute bioavailability of repaglinide administered as a tablet was 62.5% (95% CI, 49.2%-79.5%) relative to an intravenous infusion of the same dose. There was no evidence from either study that the tablet formulation led to greater variation in serum profiles of repaglinide. It was concluded that repaglinide is rapidly absorbed and eliminated in healthy subjects when administered orally or intravenously under fasting conditions, and that the total availability of repaglinide is similar in the tablet and oral solution formulations, though that the rate of absorption is slower for the tablet formulation.

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.

Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis.

PubMed

Subramanian, Raju; Zhu, Xiaochun; Hock, M Benjamin; Sloey, Bethlyn J; Wu, Benjamin; Wilson, Sarah F; Egbuna, Ogo; Slatter, J Greg; Xiao, Jim; Skiles, Gary L

2017-02-01

Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [ 14 C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting. Blood, dialysate, urine, and feces were collected to characterize the pharmacokinetics, biotransformation product profiles, mass balance, and formation of anti-etelcalcetide antibodies. Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [ 14 C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces. Biotransformation resulted from disulfide exchange with endogenous thiols, and preserved the etelcalcetide D-amino acid backbone. Drug-related radioactivity circulated primarily as serum albumin peptide conjugate (SAPC). Following removal of plasma etelcalcetide by hemodialysis, re-equilibration occurred between SAPC and L-cysteine present in blood to partially restore the etelcalcetide plasma concentrations between dialysis sessions. No unanticipated safety signals or anti-etelcalcetide or anti-SAPC antibodies were detected.

Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children.

PubMed

Visudtibhan, Anannit; Bhudhisawadi, Kasama; Vaewpanich, Jarin; Chulavatnatol, Suvatna; Kaojareon, Sming

2011-03-01

Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [(13) C8 ]-evacetrapib as a tracer.

PubMed

Cannady, Ellen A; Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G; Royalty, Jane; Ortega, Demetrio; Pack, Brian W; Begum, Syeda L; Annes, William F; Lin, Qun; Small, David S

2016-05-30

This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration-time curve (AUC) from zero to infinity (AUC[0-∞]) and to the last measureable concentration (AUC[0-tlast ]), were calculated. Bioavailability was calculated as the ratio of least-squares geometric mean of dose-normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2-47.6%) for AUC(0-∞) and 44.3% (90% CI: 41.8-46.9%) for AUC(0-tlast ). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a (13) C-labeled IV microdose tracer at about 1/1000(th) the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. © 2015 The Authors Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons Ltd.

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

Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

PubMed Central

Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

2015-01-01

Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

Recovery of fibrinogen concentrate after intraosseous application is equivalent to the intravenous route in a porcine model of hemodilution

PubMed Central

Schlimp, Christoph J.; Solomon, Cristina; Keibl, Claudia; Zipperle, Johannes; Nürnberger, Sylvia; Öhlinger, Wolfgang; Redl, Heinz; Schöchl, Herbert

2014-01-01

BACKGROUND Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration. METHODS This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry. RESULTS All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site. CONCLUSION This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would

The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease.

PubMed

Sanjay, Srinivas; Annigeri, Rajeev A; Seshadri, Rajagopalan; Rao, Budithi Subba; Prakash, Kowdle C; Mani, Muthu Krishna

2008-06-01

To compare natriuretic, kaliuretic, diuretic and free water clearance efficacy of continuous versus bolus intravenous furosemide administration in patients with chronic renal insufficiency. In a prospective randomized cross-over trial, 42 patients of chronic renal insufficiency were randomized to receive the same dose of intravenous furosemide as bolus and continuous infusion. The effects of bolus and intravenous administration of furosemide on the volume of urine, sodium and potassium excretion were assessed. Mean age was 53.6 +/- 14 years and 23 (55%) were male. The mean modification of diet in renal disease glomerular filtration rate was 20.5 +/- 17 mL/min per 1.73 m(2). The urinary excretion of sodium in intravenous bolus and infusion was 98.1 +/- 78 and 114.4 +/- 100 mmol, respectively (P = 0.001). Total urinary volume following bolus and infusion of furosemide was 1064 +/- 627 and 1170 +/- 764 mL, respectively (0.001). The excretion of potassium was similar in bolus (15.8 +/- 16.6) and infusion (14.3 +/- 9) administration (P = 0.11). The fractional excretion of sodium was higher following infusion (16.63 +/- 16.1) than bolus administration (12.87 +/- 9) of furosemide (P = 0.016). Continuous intravenous infusion of furosemide has significantly better natriuretic and diuretic effect than bolus administration of the same dose of the drug in patients with advanced chronic renal insufficiency.

A Review of Best Practices for Intravenous Push Medication Administration.

PubMed

Lenz, Janelle R; Degnan, Daniel D; Hertig, John B; Stevenson, James G

In 2015, the Institute for Safe Medication Practices (ISMP) released safe practice guidelines for adult intravenous (IV) push medications. ISMP's most recent set of guidelines has added to a growing list of recommendations from professional groups on the safe use of IV medications. These recommendations and guidelines vary with regard to their audience, scope, and terminology. In some ways, these variations may contribute to confusion and delayed adoption of the standards. This report attempts to provide clarity about the rationale and background regarding the need for practice improvement, discussion of various guidelines, and practice mitigation strategies to improve patient safety.

[Acute hepatitis following amiodarone administration].

PubMed

Tagliamonte, E; Cice, G; Ducceschi, V; Mayer, M S; Iacono, A

1997-09-01

A 61 year old man, treated with amiodarone since 1993 for resistant supraventricular arrhythmias, developed acute hepatitis after an intravenous amiodarone administration. Kidney and liver function tests were performed and pointed out abnormal results. Symptoms ascribable to hepatotoxicity were absent. These changes returned to normal levels within 20 days from withdrawal of the drug. Amiodarone hepatotoxicity can be related to prolonged therapy with a high dose. Intravenous amiodarone may cause acute hepatic disease, but it is suggested that polysorbate 80, a solvent added to the intravenous infusion, is a more likely cause of this complication.

Chemical Modification with High Molecular Weight Polyethylene Glycol Reduces Transduction of Hepatocytes and Increases Efficacy of Intravenously Delivered Oncolytic Adenovirus

PubMed Central

Doronin, Konstantin; Shashkova, Elena V.; May, Shannon M.; Hofherr, Sean E.

2009-01-01

Abstract Oncolytic adenoviruses are anticancer agents that replicate within tumors and spread to uninfected tumor cells, amplifying the anticancer effect of initial transduction. We tested whether coating the viral particle with polyethylene glycol (PEG) could reduce transduction of hepatocytes and hepatotoxicity after systemic (intravenous) administration of oncolytic adenovirus serotype 5 (Ad5). Conjugating Ad5 with high molecular weight 20-kDa PEG but not with 5-kDa PEG reduced hepatocyte transduction and hepatotoxicity after intravenous injection. PEGylation with 20-kDa PEG was as efficient at detargeting adenovirus from Kupffer cells and hepatocytes as virus predosing and warfarin. Bioluminescence imaging of virus distribution in two xenograft tumor models in nude mice demonstrated that PEGylation with 20-kDa PEG reduced liver infection 19- to 90-fold. Tumor transduction levels were similar for vectors PEGylated with 20-kDa PEG and unPEGylated vectors. Anticancer efficacy after a single intravenous injection was retained at the level of unmodified vector in large established prostate carcinoma xenografts, resulting in complete elimination of tumors in all animals and long-term tumor-free survival. Anticancer efficacy after a single intravenous injection was increased in large established hepatocellular carcinoma xenografts, resulting in significant prolongation of survival as compared with unmodified vector. The increase in efficacy was comparable to that obtained with predosing and warfarin pretreatment, significantly extending the median of survival. Shielding adenovirus with 20-kDa PEG may be a useful approach to improve the therapeutic window of oncolytic adenovirus after systemic delivery to primary and metastatic tumor sites. PMID:19469693

Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses.

PubMed

Knych, H K; Steinmetz, S J; McKemie, D S

2015-04-01

The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent. © 2014 John Wiley & Sons Ltd.

Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical practice patterns.

PubMed

Conort, Ornella; Gabardi, Steven; Didier, Marie-Pauline; Hazebroucq, Georges; Cariou, Alain

2002-04-01

To assess the knowledge of prescribers regarding intravenous to oral conversions of fluoroquinolones, the frequency and time until conversion, and to compare prescriber knowledge with the data collected concerning the reasons stated for continuation of intravenous fluoroquinolones. Prospective chart review and questionnaire. Large teaching hospital in Paris, France. Fifty-one males and females. Data were collected on in-patients receiving intravenous fluoroquinolone for at least three days and hospitalized in one of six in-patient units. Patients receiving intravenous fluoroquinolone for less than three days were excluded. A questionnaire to assess the awareness of a potential conversion was distributed to those practitioners who had patients reviewed during the data-collection phase. The questionnaire revealed the ten most common reasons for continuing intravenous administration for more than three days. However, the physicians agreed that most patients should be converted as soon as possible. Practice patterns differed, with only 17 of 51 patients actually converted to oral therapy. In theory, the clinicians were aware of when to perform the conversion. However, in practice, the frequency of conversion was lower than optimum. Changes in clinical practice are needed to decrease the costs of intravenous therapy, without jeopardizing quality of care.

Acute Hepatotoxicity of Intravenous Amiodarone: Case Report and Review of the Literature.

PubMed

Chen, Chia-Chi; Wu, Chien-Chih

2016-01-01

Amiodarone is a class III antiarrhythmic drug widely used for the treatment of both supraventricular and ventricular arrhythmias in intensive care unit. Hepatotoxicity of amiodarone is usually mild and delayed onset. Acute hepatotoxicity is a rare side effect and usually correlated to intravenous form use. In this case, acute hepatocellular injury occurred within 24 hours after the administration of intravenous amiodarone. Liver enzyme significantly improved after holding intravenous amiodarone use. Because ventricular arrhythmia persisted and side effects occurred to alternative therapy, low dose of oral amiodarone was resumed and hepatotoxicity did not occur afterward. Acute hepatotoxicity of intravenous amiodarone is possibly related to polysorbate 80, the solubilizer of amiodarone infusion or higher dose. As a result, when intravenous amiodarone is prescribed, closely monitoring liver enzyme is highly suggested. If acute hepatitis takes place secondary to intravenous amiodarone, oral therapy should not be resumed afterward. If there is no alternative treatment, lower dose of oral amiodarone (≤200 mg/d) could be tried and should monitor liver function regularly.

Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route

PubMed Central

Hokkanen, Ann-Helena; Raekallio, Marja R; Salla, Kati; Hänninen, Laura; Viitasaari, Elina; Norring, Marianna; Raussi, Satu; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

2014-01-01

Objective To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Study design Randomised, prospective clinical study. Animals Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Methods Detomidine at 80 μg kg−1 was administered to ten calves sublingually (GEL) and at 30 μg kg−1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg−1) and local anaesthetic (lidocaine 3 mg kg−1) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student's t-test and linear mixed models as relevant. Results The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL−1 (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Conclusions and clinical relevance Oromucosally administered detomidine is an effective sedative agent for calves prior to disbudding. PMID:24628898

Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis

PubMed Central

Vamvini, Maria T.; Hamnvik, Ole-Petter; Sahin-Efe, Ayse; Gavrieli, Anna; Dincer, Fadime; Farr, Olivia M.

2016-01-01

Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Main Outcome Measures: Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured. Results: Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration. Conclusions: Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract

Rapid and equivalent systemic bioavailability of the antidotes HI-6 and dicobalt edetate via the intraosseous and intravenous routes.

PubMed

Hill, Simon L; Thomas, Simon H L; Flecknell, Paul A; Thomas, Aurelie A; Morris, Chris M; Henderson, David; Dunn, Michael; Blain, Peter G

2015-08-01

Rapid and effective administration of antidotes by emergency medical responders is needed to improve the survival of patients severely poisoned after deliberate release of chemical weapons, but intravenous access is difficult to obtain while wearing personal protective equipment and in casualties with circulatory collapse. To test the hypothesis that rapid and substantial bioavailability of the antidotes HI-6 oxime and dicobalt edetate can be achieved via the intraosseous (IO) route, plasma concentration-time profiles of these antidotes were compared after administration by the intravenous and IO routes in a minipig animal model. 12 male Göttingen minipigs were randomly allocated to receive 7.14 mg/kg of HI-6 (by rapid bolus) then 4.28 mg/kg of dicobalt edetate (over 1 min) via the intravenous or IO route. Plasma concentrations of each antidote were measured over 360 min following administration and plasma concentration-time profiles plotted for each drug by each route. Peak HI-6 and cobalt concentrations occurred within 2 min of administration by both the intravenous and IO routes. Mean areas under the concentration-time curves (SD) to the end of the experiment (area under the concentration-time curve, AUC (0-t)) for cobalt were 430 (47, intravenous) and 445 (40, IO) μg-min/mL (mean difference 15, 95% CI -41 to 70, p=0.568) and for HI-6 were 2739 (1038, intravenous) and 2772 (1629, IO) μg-min/mL (mean difference 0.33, 95% CI -1724 to 1790, p=0.97). Increases in heart rate (by 50 beats/min intravenous and 27 beats/min IO) and BP, (by 67/58 mm Hg intravenous and 78/59 mm Hg IO), were observed after dicobalt edetate, consistent with the known adverse effects of this antidote. This study demonstrates rapid and similar systemic bioavailability of HI-6 and dicobalt edetate when given by the IO and intravenous routes. IO delivery of these antidotes is appropriate in the acute management of patients with organophosphate and cyanide intoxication when

An Unusual Case of Suicide Attempt Using Intravenous Injection of Kerosene.

PubMed

Hasan, M N; Sutradhar, S R; Ahmed, S M; Chowdhury, I H

2016-07-01

Kerosene belongs to the hydrocarbon group of compounds, used as a fuel for lamps, as well as heating and cooking in developing countries. Accidental kerosene poisoning and intoxication usually occur by inhalation or by occupational percutaneous absorption. Adults usually ingest kerosene for the purpose of self-harm, and children may ingest accidentally. Suicidal attempt using intravenous kerosene is an extra ordinary and very rare occurrence. A very few data are available regarding effects of intravenous administration of kerosene and its management.

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.

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration.

PubMed

Pandey, Santosh Kumar; Goyal, Vinod Kumar; Nalge, Prashant; Are, Purnachander; Vincent, Sthevaan; Nirogi, Ramakrishna

2017-12-01

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-analysis.

PubMed

Grisaru, Silviu; Xie, Jianling; Samuel, Susan; Hartling, Lisa; Tarr, Phillip I; Schnadower, David; Freedman, Stephen B

2017-01-01

The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with

A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

PubMed

Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

2013-06-01

Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

Absorption of clonazepam after intranasal and buccal administration.

PubMed Central

Schols-Hendriks, M W; Lohman, J J; Janknegt, R; Korten, J J; Merkus, F W; Hooymans, P M

1995-01-01

Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection. PMID:7640154

Intravenous methimazole in the treatment of refractory hyperthyroidism.

PubMed

Hodak, Steven P; Huang, Caroline; Clarke, Donna; Burman, Kenneth D; Jonklaas, Jacqueline; Janicic-Kharic, Natasa

2006-07-01

Management of a hyperthyroid patient unable to take oral or rectal medication is a difficult clinical problem. The need for an alternative parenteral route of antithyroid medication administration in thyrotoxic patients occurs in certain rare cases, such as emergent gastrointestinal surgery, bowel ileus or obstruction, or severe vomiting and diarrhea. We report a simple and successful protocol for the preparation and use of intravenous methimazole (MMI) for treatment of hyperthyroidism in patients intolerant of orally and rectally administered thionamides. Five hundred milligrams of methimazole USP powder was reconstituted with pH-neutral 0.9% sodium chloride solution to a final volume of 50 mL using aseptic technique, then filtered through a 0.22-microm filter. MMI injection was administered as a slow intravenous push over 2 minutes and followed by a saline flush. A 76-year-old man, intolerant of oral and rectal medications because of an ileus and intractable diarrhea, who developed worsening thyrotoxicosis after an emergent spinal cord decompression, and a 42-year-old man with chronic liver disease and hyperthyroidism, requiring emergent exploratory laparotomy and maintenance of complete bowel rest because of persistent gastrointestinal bleeding were rendered euthyroid using intravenous MMI. Two cases of hyperthyroidism successfully treated with a preparation of intravenous MMI are described.

Safety of intravenous lacosamide in critically ill children.

PubMed

Welsh, Sarah S; Lin, Nan; Topjian, Alexis A; Abend, Nicholas S

2017-11-01

Acute seizures are common in critically ill children. These patients would benefit from intravenous anti-seizure medications with few adverse effects. We reviewed the usage and effects of intravenous lacosamide in critically ill children with seizures or status epilepticus. This retrospective series included consecutive patients who received at least one dose of intravenous lacosamide from April 2011 to February 2016 in the pediatric intensive care unit of a quaternary care children's hospital, including patients with new lacosamide initiation and continuation of outpatient oral lacosamide. Dosing and prescribing practices were reviewed. Adverse effects were defined by predefined criteria, and most were evaluated during the full admission. We identified 51 intensive care unit admissions (47 unique patients) with intravenous lacosamide administration. Lacosamide was utilized as a third or fourth-line anti-seizure medication for acute seizures or status epilepticus in the lacosamide-naïve cohort. One patient experienced bradycardia and one patient experienced a rash that were considered potentially related to lacosamide. No other adverse effects were identified, including no evidence of PR interval prolongation. Lacosamide was well tolerated in critically ill children. Further study is warranted to evaluate the effectiveness of earlier lacosamide use for pediatric status epilepticus and acute seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs.

PubMed

Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

2009-08-01

To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 microl saline was administered intranasally or 250 microl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 microg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. In 96% of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration.

Successful outcome after intravenous gasoline injection.

PubMed

Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz

2007-12-01

Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

PubMed

Cosgrove, J W; Brown, I R

1984-05-01

An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration.

PubMed

Haug, Karin G; Weber, Benjamin; Hochhaus, Guenther; Butterweck, Veronika

2012-01-23

Ammi visnaga L. (syn. Khella, Apiaceae) preparations have traditionally been used in the Middle East for the treatment of kidney stone disease. Visnagin, a furanocoumarin derivative, is one of the main compounds of Ammi visnaga with potential effects on kidney stone prevention. To date, no information is available about the pharmacokinetic (PK) properties of visnagin. It was the aim of the study to characterize the PK properties of visnagin after intravenous (i.v.) bolus administration in rats and to develop an adequate model for the description of the observed data, including model parameter estimates. Therefore, three doses of visnagin (1.25, 2.5, and 5mg/kg) solubilized in 25% Captisol® were administered by i.v. bolus injection to male Sprague-Dawley rats. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Both non-compartmental and compartmental PK analyses were performed. A stepwise model building approach was applied including nonlinear mixed effect modeling for final model selection and to obtain final model estimates in NONMEM VI. The average areas under the curve (AUC(0-last)) after doses of 1.25, 2.5, and 5mg/kg were 1.03, 3.61, and 12.6 mg *h/l, respectively. The shape of the plasma concentration-time profiles and the observed disproportionate increase in AUC(0-last) with increasing dose suggested nonlinearity in the elimination of visnagin. A two-compartment Michaelis-Menten model provided the best fit with following typical values of the parameter estimates: 2.09 mg/(l*h) (V(max)), 0.08 mg/l (K(M)), 0.175 l (V(C)), 1.0 h⁻¹ (k₁₂), and 1.22 h⁻¹ (k₂₁). Associated inter-subject variability estimates (% CV) for V(max), K(M) and V(C) were 21.8, 70.9, and 9.2, respectively. Intra-subject variability (constant CV error model) was estimated to be 7.0%. The results suggest the involvement of a saturable process in the elimination of visnagin, possibly an enzyme or transporter system. Copyright © 2011

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

PubMed

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

Intravenous injection of indocyanine green results in an artificial transient desaturation by pulse oximetry.

PubMed

Ediriwickrema, Lilangi S; Francis, Jasmine H; Arslan-Carlon, Vittoria; Dalecki, Paul H; Brodie, Scott E; Marr, Brian P; Abramson, David H

2015-01-01

To describe a case series of transient oxygen desaturation measured by pulse oximetry during the intravenous infusion of indocyanine green to enhance transpupillary thermotherapy in treating retinoblastoma after ophthalmic artery chemosurgery. Retrospective descriptive case series. The intravenous administration of indocyanine green for ophthalmic angiography resulted in a transient drop in oxygen saturation as measured by Nellcor fingertip pulse oximetry in three children with retinoblastoma receiving indocyanine green-guided transpupillary thermotherapy. The magnitude of reduction ranged from 92% to 94% from an initial reading of 99% to 100% in each case, with an average duration of 3 minutes. Concurrent measurement of blood pressure, pulse, and expired CO2 showed no changes during this process. Administration of intravenous indocyanine green resulted in a transient desaturation by oximetry during transpupillary thermotherapy for children with retinoblastoma under anesthesia because of the fluorescent dye's absorption of red light in a manner similar to that of deoxygenated hemoglobin, thereby leading to transient instrument misinterpretation and miscalculation of arterial oxygenation.

Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model.

PubMed

Xanthos, Theodoros; Psichalakis, Nikolaos; Russell, David; Papalois, Apostolos; Koutsovasilis, Anastasios; Athanasopoulos, Dimitrios; Gkiokas, Georgios; Chalkias, Athanasios; Iacovidou, Nicoletta

2016-08-01

To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.

PubMed

Matsuzaki, Yasunori; Konno, Ayumu; Mochizuki, Ryuta; Shinohara, Yoichiro; Nitta, Keisuke; Okada, Yukihiro; Hirai, Hirokazu

2018-02-05

Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein (EGFP) under the control of the constitutive CBh promoter (a hybrid of cytomegalovirus early enhancer and chicken β-actin promoter). Age-matched control marmosets were treated with standard AAV9-capsid vectors. The animals were sacrificed 6 weeks after the viral injection. Based on the results, only limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV-PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia neurons. Indeed, the soma and axons in the projection from the spinal cord to the nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV-PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B transduction efficiency in the CNS of marmosets was comparable to that of AAV9 vectors. Copyright © 2017 Elsevier B.V. All rights reserved.

[Influence of iron nanoparticles on cardiac performance and hemodynamics in rabbits after intravenous administration in acute experiment].

PubMed

Doroshenko, A M

2014-01-01

Iron nanoparticles are possessed by high potential in the creation of effective and safe antianemic drugs due to the enhanced biological activity of metal nanoparticles. As a step of intravenous dosage form development the study of short-term effects of iron nanoparticles on the cardiovascular system is important. Dose-dependent changes of systemic hemodynamics' parameters were established in acute experiment on rabbits after several intravenous injections of zero-valent iron nanoparticles solution.

[Intravenous ethyl alcohol in metabolic resuscitation].

PubMed

Agolini, G; Lipartiti, T; Zaffiri, O; Musso, L; Belloni, G P

1980-11-01

Intravenously administered ethyl alcohol may be effective as analgesic and hypotensive peripheric vasoactive drug. In the Intensive Care Departments parenteral ethanol administration is infrequent because no "sure dosage" can be suggested in adults and children. Liver, kidney and C.N.S. diseases can worsen; foetopathy can follow. Drug-ethanol interaction may be particularly important for some patients admitted in Intensive Care Departments. Often the potential caloric support cannot be fully utilized ("empty" calories) and seldom hyperventilation, hyperlactacidemia and impaired protein synthesis can follow.

Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps.

PubMed

Manrique-Rodríguez, S; Sánchez-Galindo, A C; Fernández-Llamazares, C M; Calvo-Calvo, M M; Carrillo-Álvarez, Á; Sanjurjo-Sáez, M

2016-10-01

To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. A tertiary level hospital pediatric intensive care unit. Infusions delivered with infusion pumps in all pediatric intensive care unit patients. Design of a drug library with safety limits for all intravenous drugs prescribed. Users' compliance with drug library as well as number and type of errors prevented were analyzed. Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Compliance with a pediatric clinical practice guideline for intravenous fluid and electrolyte administration.

PubMed

Hurdowar, Amanda; Urmson, Lynn; Bohn, Desmond; Geary, Denis; Laxer, Ronald; Stevens, Polly

2009-01-01

The occurrence of acute hyponatremia associated with cerebral edema in hospitalized children has been increasingly recognized, with over 50 cases of neurological morbidity and mortality reported in the past decade. This condition most commonly occurs in previously healthy children where maintenance intravenous (IV) fluids have been prescribed in the form of hypotonic saline (e.g., 0.2 or 0.3 NaCl). In response to similar problems at The Hospital for Sick Children (six identified through hospital morbidity and mortality reviews and safety reports prior to fall 2007), an interdisciplinary clinician group from our institution developed a clinical practice guideline (CPG) to guide fluid and electrolyte administration for pediatric patients. This article reviews the evaluation of one patient safety improvement to change the prescribing practice for IV fluids in an acute care pediatric hospital, including the removal of the ability to prescribe hypotonic IV solutions with a sodium concentration of < 75 mmol/L. The evaluation of key components of the CPG included measuring practice and process changes pre- and post-implementation. The evaluation showed that the use of restricted IV fluids was significantly reduced across the organization. Success factors of this safety initiative included the CPG development, forcing functions, reminders, team engagement and support from the hospital leadership. A key learning was that a project leader with considerable dedicated time is required during the implementation to develop change concepts, organize and liaise with stakeholders and measure changes in practice. This project highlights the importance of active implementation for policy and guideline documents.

Intravenous zoledronate for osteoporosis: less might be more

PubMed Central

Grey, Andrew

2016-01-01

Annual administration of 5 mg intravenous zoledronate is moderately effective in reducing fracture risk in older adults, decreasing the relative risk of clinical fracture by 33%. However, almost 10 years after its approval for use in clinical practice there remain very substantial uncertainties about the optimal treatment regimen, that is, the lowest dose and/or longest dosing interval that is efficacious. Several pieces of clinical research suggest that the current recommendation for annual administration of 5 mg zoledronate might represent overtreatment. Clinical trials to clarify the optimal use of zoledronate for reduction of fracture risk should be undertaken. PMID:27493690

Intravenous zoledronate for osteoporosis: less might be more.

PubMed

Grey, Andrew

2016-08-01

Annual administration of 5 mg intravenous zoledronate is moderately effective in reducing fracture risk in older adults, decreasing the relative risk of clinical fracture by 33%. However, almost 10 years after its approval for use in clinical practice there remain very substantial uncertainties about the optimal treatment regimen, that is, the lowest dose and/or longest dosing interval that is efficacious. Several pieces of clinical research suggest that the current recommendation for annual administration of 5 mg zoledronate might represent overtreatment. Clinical trials to clarify the optimal use of zoledronate for reduction of fracture risk should be undertaken.

Intravenous immunoglobulin therapy for severe Clostridium difficile colitis

PubMed Central

Salcedo, J; Keates, S; Pothoulakis, C; Warny, M; Castagliuolo, I; LaMont, J; Kelly, C

1997-01-01

Background—Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. 
Aims—To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. 
Patients—Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200-300 mg/kg). 
Methods—Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. 
Results—Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4-1.6 mg/ml. 
Conclusion—Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration. 

 Keywords: Clostridium difficile; toxin; diarrhoea; IgG; immunotherapy; antibiotic PMID:9378393

Intravenous insertion site protection: moisture accumulation in intravenous site protectors.

PubMed

Lee, W E; Vallino, L M

1996-01-01

Stabilizing the intravenous catheter after insertion is a significant part of intravenous therapy. Dislodgments of the cannula from its optimal position in the vein can lead to complications such as phlebitis, thrombophlebitis, infiltration, and infection. Intravenous site protector shields are designed to protect the catheter from impact and tissue trauma at the insertion site. Nurses have requested ventilation in these shields to avoid moisture build up that may increase the risk of infections. To address this issue, experimental laboratory testing was performed to determine if moisture accumulation as evidenced by increased weight of the shield and visible evidence of condensation occurred. No moisture condensation problems with the ventilated intravenous site protectors were found.

Synthetic Strategies for Engineering Intravenous Hemostats

PubMed Central

Chan, Leslie W.-G.; White, Nathan J.; Pun, Suzie H.

2015-01-01

While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods of restoring hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf-life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin crosslinking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This review explores intravenous hemostats under development and strategies to optimize their clotting activity. PMID:25803791

The Reinforcing Effects of Nicotine in Humans and Nonhuman Primates: A Review of Intravenous Self-Administration Evidence and Future Directions for Research.

PubMed

Goodwin, Amy K; Hiranita, Takato; Paule, Merle G

2015-11-01

Cigarette smoking is largely driven by the reinforcing properties of nicotine. Intravenous (IV) self-administration procedures are the gold standard for investigating the reinforcing effects of psychoactive drugs. The goal of this review was to examine the results of published investigations of the reinforcing effects of nicotine measured using IV self-administration procedures in humans and nonhuman primates. The body of literature using nonhuman primate subjects indicates nicotine functions as a positive reinforcer when available for self-administration via IV catheters. However, it can also be difficult to establish IV nicotine self-administration in nonhuman primates and sometimes supplemental strategies have been required (e.g., priming injections or food deprivation) before subjects acquire the behavior. Although the body of literature using human subjects is limited, the evidence indicates nicotine functions as a reinforcer via the IV route of administration in adult cigarette smokers. Rates of nicotine self-injection can be variable across subjects and responding is sometimes inconsistent across sessions in both humans and nonhuman primates. The Family Smoking Prevention and Tobacco Control Act, enacted in 2009, gave the Food and Drug Administration regulatory authority over the manufacture, marketing, and distribution of tobacco products. Research examining the threshold reinforcing doses for initiation and maintenance of nicotine self-administration, comparisons of the reinforcing effects of nicotine in adolescent versus adult subjects, investigations of gender differences in the reinforcing effects of nicotine, and studies of the abuse liability of non-nicotine tobacco product constituents and their ability to alter the reinforcing effects of nicotine will inform potential tobacco regulatory actions. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2015. This work is written by (a) US Government employee

PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION

PubMed Central

Yuile, C. L.; Bly, C. G.; Stewart, W. B.; Izzo, A. J.; Wells, J. C.; Whipple, G. H.

1949-01-01

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron—deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron. Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron. Radioiron appears only in traces in abscess exudates. Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs. The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia. PMID:18140660

Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels.

PubMed

Wasfi, I A; Boni, N S; Abdel Hadi, A; Elghazali, M; Zorob, O; Alkatheeri, N A; Barezaiq, I M

1998-06-01

The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean +/- SEM) for the low and high dose, respectively, were as follows: The elimination half-lives (t1/2 beta) were 3.76 +/- 0.24 and 4.08 +/- 0.49 h, the steady state volumes of distribution (Vdss) were 320.61 +/- 38.53 and 348.84 +/- 35.36 mL/kg body weight, total body clearances (ClT) were 88.96 +/- 6.63 and 84.86 +/- 4.95 mL/h/kg body weight and renal clearances (Clr) were 0.52 +/- 0.09 and 0.62 +/- 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Code of Federal Regulations, 2013 CFR

2013-04-01

... delivery systems other than oral or intravenous dosage forms with an appropriate reference standard, the... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study. 320.26 Section 320.26 Food and Drugs FOOD AND DRUG ADMINISTRATION...

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Code of Federal Regulations, 2012 CFR

2012-04-01

... delivery systems other than oral or intravenous dosage forms with an appropriate reference standard, the... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study. 320.26 Section 320.26 Food and Drugs FOOD AND DRUG ADMINISTRATION...

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Code of Federal Regulations, 2014 CFR

2014-04-01

... delivery systems other than oral or intravenous dosage forms with an appropriate reference standard, the... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study. 320.26 Section 320.26 Food and Drugs FOOD AND DRUG ADMINISTRATION...

Observations on intravenous administration of lignocaine in patients with myocardial infarction.

PubMed Central

Campbell, N P; Kelly, J G; Adgey, A A; McDevitt, D G; Pantridge, J F

1978-01-01

Lignocaine was administered intravenously to 36 patients with acute myocardial infarction. A bolus of 100 mg followed by an infusion of 2 mg/minute failed to maintain plasma levels above 2 microgram/ml. A bolus of 100 mg followed by 4 mg/minute also failed to maintain satisfactory plasma concentrations during the first hour of therapy. A bolus of 75 mg was combined with an infusion of 10 mg/minute for 20 minutes followed by 1.5 mg/minute. Satisfactory plasma concentrations during the first hour were observed in 94 per cent of the estimations. No important adverse side effects occurred during the infusion of 10 mg/minute. PMID:737094

A Study of Intravenous Administration of Vitamin C in the Treatment of Acute Herpetic Pain and Postherpetic Neuralgia

PubMed Central

Kim, Min Sung; Kim, Dong Jin; Na, Chan Ho

2016-01-01

Background Although there are several available management strategies for treatment of both acute pain of herpes zoster (HZ) and postherpetic neuralgia (PHN), it is difficult to treat them adequately. Objective The aim of this study was to evaluate the efficacy of intravenously administrated vitamin C on acute pain and its preventive effects on PHN in patients with HZ. Methods Between September 2011 and May 2013 eighty-seven patients who were admitted for HZ were assessed according to age, sex, underlying diseases, duration of pain and skin lesion, dermatomal distribution, and PHN. It was a randomized controlled study, in which 87 patients were randomly allocated into the ascorbic acid group and control group. Each patient received normal saline infusion with or without 5 g of ascorbic acid on days 1, 3, and 5 then answered questionnaires that included side effects and pain severity using visual analogue scale on days 1, 2, 3, 4, and 5. After discharge, the severity of pain was obtained at out-patient clinic or by telephone on weeks 2, 4, 8, and 16. Results There was no differences in severity of pain on patients' age, sex, underlying diseases, duration of pain and skin lesion and dermatomal distribution between two groups (p>0.05). Since 8th week, pain score in ascorbic acid treatment group was significantly lower than control group (p <0.05). The incidence of PHN was significantly lower in the treatment group compared to control group (p=0.014). The changes of overall pain score was significantly different between the two groups (p<0.05). Conclusion Intravenously administered ascorbic acid did not relieve acute HZ pain; but is effective for reducing the incidence of PHN. PMID:27904265

Transareolar Single-Port Needlescopic Thoracic Sympathectomy Under Intravenous Anesthesia Without Intubation: A Randomized Controlled Trial.

PubMed

Chen, Jianfeng; Du, Quan; Lin, Min; Lin, Jianbo; Li, Xu; Lai, Fancai; Tu, Yuanrong

2016-12-01

Transareolar single-port needlescopic thoracic sympathectomy under intravenous anesthesia without intubation has rarely been attempted in managing primary palmar hyperhidrosis (PPH). The objective of this study is to evaluate the feasibility and safety of this minimally invasive technique. From May 2012 to May 2015, 168 male patients with severe PPH underwent single-port endoscopic thoracic sympathectomy (ETS) and were randomly allocated to groups A or B. Patients in group A underwent nonintubated transareolar ETS with a 2-mm needle endoscope, while those in group B underwent intubated transaxillary ETS with a 5-mm thoracoscope. All procedures were performed successfully. The palms of all patients became dry and warm immediately after surgery. The mean resuscitation time was significantly shorter in nonintubated patients than in intubated patients. Postoperative sore throat occurred in 4 patients in group A and in 32 patients in group B (P < .01). The mean incision length was significantly shorter in group A than in group B. The mean postoperative pain scores were markedly higher in group B than in group A. The mean cost of anesthesia was considerably lower in nonintubated patients than in intubated patients. The mean cosmetic scores were higher in group A than in group B (P < .01). Nonintubated transareolar single-port ETS with a needle endoscope is a safe, effective, and minimally invasive therapeutic procedure, which allows a smaller incision with less pain and excellent cosmetic results. This novel procedure can be performed in a routine clinical practice for male patients with severe PPH.

The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

PubMed

Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

2010-01-01

the administration of high doses as a single infusion or bolus injection, which will enhance the cost-effectiveness and convenience of iron replacement therapy. In conclusion, FCM has many of the characteristics of an ideal intravenous iron preparation.

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…

Pharmacokinetics of intravenous and subcutaneous cefovecin in alpacas.

PubMed

Cox, S; Sommardahl, C; Seddighi, R; Videla, R; Hayes, J; Pistole, N; Hamill, M; Doherty, T

2015-08-01

The purpose of this study was to determine the pharmacokinetics of cefovecin after intravenous and subcutaneous dose of 8 mg/kg to alpacas. Bacterial infections requiring long-term antibiotic therapy such as neonatal bacteremia, pneumonia, peritonitis, dental, and uterine infections are a significant cause of morbidity and mortality in this species. However, few antimicrobials have been evaluated and proven to have favorable pharmacokinetics for therapeutic use. Most antimicrobials that are currently used require daily injections for many days. Cefovecin is a long-acting cephalosporin that is formulated for subcutaneous administration, and its long-elimination half-life allows for 14-day dosing intervals in dogs and cats. The properties of cefovecin may be advantageous for medical treatment of camelids due to its broad spectrum, route of administration, and long duration of activity. Pharmacokinetic evaluation of antimicrobial drugs in camelids is essential for the proper treatment and prevention of bacterial disease, and to minimize development of antibiotic resistant bacterial strains due to inadequate antibiotic concentrations. Cefovecin mean half-life, volume of distribution at steady-state, and clearance after intravenous administration were 10.3 h, 86 mL/kg, and 7.07 mL·h/kg. The bioavailability was 143%, while half-life, C(max), and T(max) were 16.9 h, 108 μg/mL, and 2.8 h following subcutaneous administration. In the absence of additional microbial susceptibility data for alpaca pathogens, the current cefovecin dosage regimen prescribed for dogs (8 mg/kg SC every 14 days) may need to be optimized for the treatment of infections in this species. © 2014 John Wiley & Sons Ltd.

Bailout intravenous esmolol for heart rate control in cardiac computed tomography angiography.

PubMed

Aguiar Rosa, Sílvia; Ramos, Ruben; Marques, Hugo; Santos, Rosana; Leal, Cecília; Casado, Helena; Saraiva, Márcia; Figueiredo, Luísa; Cruz Ferreira, Rui

2016-12-01

To evaluate the efficacy and safety of a heart rate (HR) reduction protocol using intravenous esmolol as bailout for failed oral metoprolol regimens in patients undergoing coronary computed tomography angiography (CCTA) with 64-slice multidetector computed tomography (64-MDCT). Patients who underwent cardiac 64-MDCT in a single institution between 2011 and 2014 were analyzed. Those with HR above 60 beats per minute (bpm) on presentation received oral metoprolol (50-200 mg) at least one hour before CCTA. Intravenous esmolol 1-2 mg/kg was administered as a bolus whenever HR remained over 65 bpm just before imaging. The primary efficacy endpoint was HR <65 bpm during CCTA. The primary safety endpoint was symptomatic hypotension or bradycardia up to hospital discharge. During the study period CCTA was performed in 947 cases. In 86% of these, oral metoprolol was the only medication required to successfully reduce HR <60 bpm. Esmolol was used in the remaining 130 patients (14%). For esmolol-treated patients mean baseline and acquisition HR were 74±14 bpm and 63±9 bpm, respectively (p<0.001). The target HR of <65 bpm was achieved in 82 of the 130 esmolol-treated patients (63%). Considering the whole population, esmolol use led to a significant increase in the primary efficacy endpoint from 86% to 95% (p<0.001). Esmolol also resulted in a statistically, but not clinically, significant reduction in systolic blood pressure (144±22 to 115±17 mmHg; p<0.001). The combined primary safety endpoint was only observed in two (1.5%) patients. Despite optimal use of oral beta-blockers, 14% of patients needed intravenous esmolol for HR control. The pre-medication combination of oral metoprolol and on-demand administration of intravenous esmolol was safe and effective and enabled 95% of patients to be imaged with HR below 65 bpm. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

PubMed

Czoty, Paul W; Nader, Michael A

2015-03-13

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.

Effects of humerus intraosseous versus intravenous amiodarone administration in a hypovolemic porcine model.

PubMed

Holloway, Cpt Monica M; Jurina, Cpt Shannan L; Orszag, Cpt Joshua D; Bragdon, Lt George R; Green, Lt Rustin D; Garcia-Blanco, Jose C; Benham, Brian E; Adams, Ltc Timothy S; Johnson, Don

2016-01-01

To compare the effects of amiodarone administration by humerus intraosseous (HIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to maximum concentration (Tmax), maximum plasma drug concentration (Cmax), time to ROSC, and mean concentrations over time in a hypovolemic cardiac arrest model. Prospective, between subjects, randomized experimental design. TriService Research Facility. Yorkshire-cross swine (n = 28). Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the HIO or the IV route. Blood samples were collected over 5 minutes. The samples were analyzed using high-performance liquid chromatography tandem mass spectrometry. ROSC, Tmax, Cmax, time to ROSC, and mean concentrations over time. There was no difference in ROSC between the HIO and IV groups; each had five achieve ROSC and two that did not (p = 1). There was no difference in Tmax (p = 0.501) or in Cmax between HIO and IV groups (p = 0.232). Means ± standard deviations in seconds were 94.3 ± 78.3 compared to 115.7 ± 87.3 in the IV versus HIO groups, respectively. The mean ± standard deviation in nanograms per milliliter for the HIO was 49,041 ± 21,107 and 74,258 ± 33,176 for the IV group. There were no significant differences between the HIO and IV groups relative to time to ROSC (p = 0.220). A repeated analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p > 0.05). The humerus intraosseous provides rapid and reliable access to administer life-saving medications during cardiac arrest.

Efficacy, Safety and Anticancer Activity of Protein Nanoparticle-Based Delivery of Doxorubicin through Intravenous Administration in Rats

PubMed Central

Golla, Kishore; Cherukuvada, Bhaskar; Ahmed, Farhan; Kondapi, Anand K.

2012-01-01

Background and Aims Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC). The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity. Methods Doxorubicin loaded apotransferrin (Apodoxonano) and lactoferrin nanoparticles (Lactodoxonano) were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA) in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers. Results In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g). Both nanoformulations showed higher localization compared to doxorubicin (Doxo) when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g) were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g), suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation. Conclusion Drug delivery through nanoformulations not

Pharmacokinetic Interpretation of Cephradine Levels in Serum After Intravenous and Extravascular Administration in Humans

PubMed Central

Rattie, Elisabeth S.; Bernardo, Peter D.; Ravin, Louis J.

1976-01-01

Pharmacokinetic parameters were calculated from intravenous data based upon a two-compartment open model. These parameters were subsequently used to determine the absorption rates and bioavailability of cephradine administered intramuscularly and orally. The results indicate that cephradine obeys dose-independent kinetics and that biological availability is complete from all dosage forms. PMID:984770

Single administration of intra-articular bupivacaine in arthroscopic knee surgery: a systematic review and meta-analysis.

PubMed

Sun, Qi-Bin; Liu, Shi-Dong; Meng, Qin-Jun; Qu, Hua-Zheng; Zhang, Zheng

2015-02-10

Single administration of intra-articular (IA) bupivacaine for pain relief after arthroscopic knee surgery is effective, but its active duration and dose-response relationship is unclear. We conducted this meta-analysis to summarize all published randomized controlled trials (RCTs), thus providing the most recent information on the safety and efficacy of single-administration IA bupivacaine for pain relief after arthroscopic knee surgery, and to determine whether a dose-response relationship exists. A systematic electronic literature search (through April 2014) was conducted to identify those RCTs that addressed the safety and efficacy of a single administration of IA bupivacaine for pain management after arthroscopic knee surgery. Subgroup analysis was conducted to determine changes in visual analog scale (VAS) scores at seven postoperative time points. Meta-regression and subgroup analyses were carried out to assess the effects of various treatment factors on efficacy and to evaluate the dose-response relationship of bupivacaine. Weighted mean differences or relative risks were calculated and pooled using a random-effects model. Twenty-eight trials involving 1,560 patients who underwent arthroscopic knee surgery met the inclusion criteria. The trials were subject to medium risk of bias. VAS scores at 2, 4, 6, 12, and 24 h postoperatively were significantly lower, the number of patients requiring supplementary analgesia was smaller, and the time to first request for analgesia was longer in the IA bupivacaine group than in the placebo group. The analgesic effect of single-administration IA bupivacaine may be associated with the effect of concomitant administration of epinephrine and concentration of bupivacaine, and no dose-response relationship was identified. No significant difference in side effects was detected between groups. Current evidence shows that the use of single-administration IA bupivacaine is effective for postoperative pain management in patients

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.

Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs.

PubMed

LeBlanc, Amy K; Naik, Shruthi; Galyon, Gina D; Jenks, Nathan; Steele, Mike; Peng, Kah-Whye; Federspiel, Mark J; Donnell, Robert; Russell, Stephen J

2013-12-01

VSV-IFNβ-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFNβ-NIS administration in dogs with naturally occurring cancer. In support of this, we executed a dose-escalation study in purpose-bred dogs to determine the maximum tolerated dose (MTD) of systemic VSV-hIFNβ-NIS, characterize the adverse event profile, and describe routes and duration of viral shedding in healthy, immune-competent dogs. The data indicate that an intravenous dose of 10(10) TCID50 is well tolerated in dogs. Expected adverse events were mild to moderate fever, self-limiting nausea and vomiting, lymphopenia, and oral mucosal lesions. Unexpected adverse events included prolongation of partial thromboplastin time, development of bacterial urinary tract infection, and scrotal dermatitis, and in one dog receiving 10(11) TCID50 (10 × the MTD), the development of severe hepatotoxicity and symptoms of shock leading to euthanasia. Viral shedding data indicate that detectable viral genome in blood diminishes rapidly with anti-VSV neutralizing antibodies detectable in blood as early as day 5 postintravenous virus administration. While low levels of viral genome copies were detectable in plasma, urine, and buccal swabs of dogs treated at the MTD, no infectious virus was detectable in plasma, urine, or buccal swabs at any of the doses tested. These studies confirm that VSV can be safely administered systemically in dogs, justifying the use of oncolytic VSV as a novel therapy for the treatment of canine cancer.

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

PubMed Central

Wang, Wen; Jin, Minghua; Du, Zhongjun; Li, Yanbo; Duan, Junchao; Yu, Yongbo; Sun, Zhiwei

2013-01-01

This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. PMID:23593469

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs.

PubMed

Fantoni, D T; Auler Junior, J O; Futema, F; Cortopassi, S R; Migliati, E R; Faustino, M; de Oliveira, C M

1999-11-01

To determine effects of i.v. administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Prospective, randomized, clinical study. 14 client-owned dogs with septic shock secondary to pyometra. Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, i.v.) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], i.v.) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to > 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs.

Intravenous support for the patient in sickle cell crisis.

PubMed

Odesina, V

2001-01-01

Sickle cell episodes (otherwise known as crises) are inevitable complications of sickle cell disease (SCD). Successful management of these episodes includes hydration, medication administration, and blood transfusion. Intravenous support is an essential component in the management of sickle cell-related complications. This article gives an overview of SCD and its complications and treatments, focusing on infusion therapy support of the patient during a sickle cell episode.

77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model.

PubMed

Carreiro, Stephanie; Blum, Jared; Hack, Jason B

2014-07-01

We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

[Features of bemithyl pharmacokinetics upon inhalation administration].

PubMed

Kurpiakova, A F; Geĭbo, D S; Bykov, V N; Nikiforov, A S

2014-01-01

A comparative study of bemithyl pharmacokinetics was carried out upon its inhalation, intragastric and intravenous administration. The main drug metabolites were identified and the pharmacokinetic parameters were calculated. The obtained results suggest that the inhalation administration of bemithyl is a promising replacement for oral administration, which is related to high bioavailability of the drug and the absence of the effect of "first pass" through the liver.

Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats.

PubMed

Lee, Soo-Han; Kim, Seung-Hyun; Noh, Yook-Hwan; Choi, Byung-Moon; Noh, Gyu-Jeong; Park, Woo-Dae; Kim, Eun-Jung; Cho, Ik-Hyun; Bae, Chun-Sik

2016-02-01

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple- or single-dose oral and transdermal administration. Venous blood was collected at preset intervals in single- and multiple-dose studies. Non-compartmental pharmacokinetics was analysed for all formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and 8.21 ± 0.89 mg/kg, respectively. The maximum plasma concentration was lower and the half-life longer after patch administration than oral and IV administration. Memantine bioavailability was 41 and 63% for oral and patch administration, respectively. Steady state was achieved around 24 hr for oral and patch administration. The mean AUC increased after oral or patch administration from single to multiple dose. The memantine patch formulation displayed a longer duration of action and lower peak plasma concentration. However, drug exposure was similar to the oral formulation at each dose. Additionally, the memantine patch formulation displayed a smaller interindividual variability and lower accumulation than the oral formulation. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Intravenous vaiproate therapy.

PubMed

Shah, Nilesh; Shenoy, Sujit; Gawde, Pradnya

2003-10-01

Four cases of acute manic episode (bipolar-l disorder), not responding to oral valproate or other mood stabilizer and neuroleptics were given injection valproate intravenously. Three out of 4 patients showed good response and tolerance to intravenous valporate.

A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

PubMed Central

Gallimore, Andrew R.; Strassman, Rick J.

2016-01-01

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 min—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent. PMID:27471468

A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience.

PubMed

Gallimore, Andrew R; Strassman, Rick J

2016-01-01

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel "alternate universe," often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient "beings." The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.

PubMed

Wasan, Kishor M; Risovic, Verica; Sivak, Olena; Lee, Stephen D; Mason, Douglas X; Chiklis, Gregory R; McShane, Jim; Lynn, Melvyn; Wong, Nancy; Rossignol, Daniel P

2008-01-01

Eritoran (E5564) is a glycophospholipid that acts as a toll-like receptor 4 (TLR4) antagonist that is being tested as a treatment for severe sepsis and septic shock. In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic (PD) effects in vivo. The purpose of this study was to determine the influence of changes in plasma cholesterol and triglyceride concentrations on the plasma pharmacokinetics and ex vivo activity of eritoran following single intravenous bolus dosing of eritoran to healthy female rabbits fed either a regular chow diet or a cholesterol-enriched diet. This was done with eritoran administered as stable micelle formulations of mean hydrodynamic diameters of 8 or 27 nm). Female New Zealand White rabbits were fed a standard diet for 7 days and then randomly assigned either a regular chow diet [regular-diet (n = 9)] or a cholesterol-enriched diet [cholesterol-diet (n = 12)] for an additional 7 days. Following feeding of these diets a single intravenous bolus dose of eritoran (0.5 mg/kg) formulated into either "small micelles" (8 nm in diameter) or "large micelles" (27 nm in diameter) was administered to regular-fed and cholesterol-fed rabbits. Serial blood samples were obtained prior to eritoran administration and at the following times post injection: 0.083 (5 min), 1, 2, 4, 8, 10, 24, 48 and 72 h. Plasma was analyzed for eritoran concentrations using LC/MS/MS. Total plasma cholesterol (TC) and triglyceride (TG) levels were quantified using enzymatic kits. Plasma eritoran pharmacokinetic (PK) parameters were estimated by non-compartmental analysis using the WinNonlin nonlinear estimation program. To analyze PD activity, whole blood obtained at 0.083 (5 min), 2, 24, 48 and 72 h following eritoran administration was assessed for ex vivo activity by measuring the ability of 1 and 10 ng/ml LPS to elicit TNF-alpha release. Total plasma cholesterol and triglyceride levels were significantly higher in cholesterol

Pharmacokinetics of pidotimod in broiler chickens by UHPLC-MS/MS after oral and intravenous administration.

PubMed

Zhang, Ruili; Qiu, Mei; Zhao, Li; Cui, Liangliang; Wang, Chunyuan; Zhu, Jiajia; Hao, Zhihui

2018-03-01

Pidotimod is widely used in children as an immune promoter but it has not been fully evaluated in animals. The pharmacokinetics of pidotimod and its oral bioavailability have not been described in broiler chickens. We developed a simple and sensitive UHPLC-MS/MS assay for rapid determination of pidotimod levels in chicken blood. Recoveries were nearly 100% and the coefficients of accuracy and precision were minimal. Healthy broiler chickens were given 10 mg/kg pidotimod either orally or intravenously. The oral pidotimod was rapidly absorbed (time to reach maximum concentration, 1.25 h) and rapidly eliminated (the mean residence time was 3.2 h). A noncompartmental analysis of the intravenous route indicated a mean plasma clearance of 2.2 L (h kg) -1 with an estimated mean volume of distribution at steady state of 12.69 L/kg. The bioavailability of pidotimod after oral dosing was 27%. Copyright © 2017 John Wiley & Sons, Ltd.

Is combined topical and intravenous tranexamic acid superior to single use of tranexamic acid in total joint arthroplasty?

PubMed Central

Yang, Liqing; Du, Shuai; Sun, Yuefeng

2017-01-01

Abstract Background: To compare the efficacy and safety of the combined application of both intravenous and topical tranexamic acid (TXA) versus the single use of either application in patients with total knee and hip arthroplasty (TKA and THA). Methods: Potentially relevant studies were identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, and the Cochrane Library. Randomized control trials (RCTs) of patients prepared for total joint arthroplasty that compared combined TXA with placebo were retrieved. The primary endpoint was hemoglobin decline or postoperative hemoglobin level, blood loss, drainage volume, transfusion requirements. The secondary outcomes were length of stay (LOS), and operation time as well as surgery-related adverse effects, such as wound infection, deep vein thrombosis (DVT), and pulmonary embolism (PE). After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. Results: Five RCTs that included 604 patients met the inclusion criteria. The present meta-analysis indicated significant differences existed in the total blood loss (mean difference [MD] = −134.65, 95% CI: −191.66 to −77.64, P < .0001), postoperative hemoglobin level (MD = 0.74, 95% CI: 0.39–1.10, P < .0001), drainage volume (MD = −47.44, 95% CI: −64.55 to −30.33, P < .00001), and transfusion rate (risk difference [RD] = −0.06, 95% CI: −0.10 to −0.02, P = .006) between groups. Conclusion: Combined administration of TXA in TKA and THA was associated with significantly reduced total blood loss, postoperative hemoglobin decline, drainage volume, and transfusion requirements. Well-designed, high-quality RCTs with long-term follow-up are still required. PMID:28746213

[Superantigens and toxic shock syndrome. A report of three cases treated with intravenous gammaglobulin].

PubMed

Vázquez García, Rubén Eduardo; Hernández Bautista, Víctor; Espinosa Padilla, Sara

2006-01-01

The superantigens cause a massive polyclonal activation of T-cells, producing an immense liberation of proinflamatory cytokines, which induces the clinical data of toxic shock syndrome. In international studies the administration of polyclonal intravenous gammaglobulin has been observed to diminish the mortality 50 to 20%. But at the present it has not been reported in Mexico the clinical effectiveness of this therapeutic modality in toxic shock syndrome. We report three cases of toxic shock syndrome treated with gammaglobulin intravenous, and we describe their favorable clinical evolution.

Intravenous injection of beta-amyloid seeds promotes cerebral amyloid angiopathy (CAA).

PubMed

Burwinkel, Michael; Lutzenberger, Manuel; Heppner, Frank L; Schulz-Schaeffer, Walter; Baier, Michael

2018-03-05

Seeding and spread of beta-amyloid (Aβ) pathologies have been considered to be based on prion-like mechanisms. However, limited transmissibility of Aβ seeding activity upon peripheral exposure would represent a key difference to prions, not only in terms of pathogenesis but also in terms of potential transmission of disease. We partially characterized the seeded Aβ amyloidosis after intracerebral injection of various brain homogenates in APP/PS1 mice. One particularly seed-laden homogenate was selected to investigate the development of Aβ pathologies after intravenous exposure. We report here that a single intravenous injection of an Alzheimer disease patient's-brain extract into APP/PS1 recipient mice led to cerebral amyloid angiopathy within 180 days post injection. Thus, vascular proteinopathies such as CAA are transmissible in mice via the intravenous route of peripheral exposure.

Intravenous Vaiproate Therapy

PubMed Central

Shah, Nilesh; Shenoy, Sujit; Gawde, Pradnya

2003-01-01

Four cases of acute manic episode (bipolar-l disorder), not responding to oral valproate or other mood stabilizer and neuroleptics were given injection valproate intravenously. Three out of 4 patients showed good response and tolerance to intravenous valporate. PMID:21206868

Hypotensive effect of alpha-lipoic acid after a single administration in rats.

PubMed

Dudek, Magdalena; Razny, Katarzyna; Bilska-Wilkosz, Anna; Iciek, Malgorzata; Sapa, Jacek; Wlodek, Lidia; Filipek, Barbara

2016-05-01

The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter. Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

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

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers.

PubMed

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-11-01

The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. © 2014 The British Pharmacological Society.

Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

PubMed Central

Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

2014-01-01

Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

Results of intravenous steroid injection on reduction of postoperative edema in rhinoplasty.

PubMed

Alajmi, Monther Ali; Al-Abdulhadi, Khalid A; Al-Noumas, Hamoud Saud; Kavitha, Gopalan

2009-12-01

To determine the efficacy of intravenous dexamethasone in reducing postrhinoplasty edema. A prospective, randomized clinical trial with placebo control. Department of Otorhinolaryngology, Al-Sabah and Zain Hospital, Kuwait. Eighty-four patients (male = 28; female = 56) aged between 20 and 40 years, undergoing open rhinoplasty with hump removal and bilateral lateral osteotomies were enrolled in this study. Patients were randomized to receive two doses of 10 mg of dexamethasone intravenously or placebo, first dose during surgery and second dose 12 hours after surgery. Patients were evaluated postoperatively at 24 hours, days 2, 5, 7 and 10 for periorbital edema. 10 mg of dexamethasone given intravenously during rhinoplasty and a second dose 12 hours after surgery, reduced postoperative periorbital edema significantly. This study showed a statistically significant benefit of dexamethasone over placebo in reducing periorbital edema after rhinoplasty. No complications were attributed to the administration of dexamethasone.

Chemical and physical compatibility of an intravenous solution of epinephrine with calcium chloride.

PubMed

Weeks, Phillip A; Teng, Yang; Wu, Lei; Sun, Mary; Yang, Zhen; Chow, Diana S-L

2014-01-01

An infusion of epinephrine combined with calcium chloride has been used historically as an intravenous inotropic solution to support critically ill heart failure patients with severe cardiogenic shock. There is no reliable data on the stability of this solution beyond three hours. This study was conducted to evaluate the chemical and physical compatibility of epinephrine (0.032 mg/mL) combined with calcium chloride (4 mg/mL) in a solution for intravenous administration up to 26 hours at room temperature. The chemical stability of epinephrine was monitored by measuring epinephrine concentrations using high-performance liquid chromatography. The physical compatibility of the mixture was determined by measuring spectrophotometric absorbance between 400 to 700 nm. Absorbance greater than 0.010 AU was considered an indicator of the presence of precipitation. The results showed epinephrine with calcium chloride was stable together in normal saline up to 26 hours at room temperature, irrespective of exposure to light. The absorbance of epinephrine throughout the study was less than 0.010 AU, indicating no significant precipitation. Conclusions indicate that epinephrine (0.032 mg/mL) combined with calcium chloride (4 mg/mL) in normal saline at room temperature is acceptably stable up to 26 hours for intravenous administration.

Schedule Dependence in Cancer Therapy: Intravenous Vitamin C and the Systemic Saturation Hypothesis

PubMed Central

Miranda Massari, Jorge R.; Duconge, Jorge; Riordan, Neil H.; Ichim, Thomas

2013-01-01

Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do single continuous IV doses of the same total exposure. This approach would be expected to minimize saturation of renal reabsorption, providing a continuous “dynamic flow” of vitamin C in the body for optimal systemic exposure and clinical outcomes. This prevents the “systemic saturation” phenomena, which may recycle vitamin C and render it less effective as an anticancer agent. Nonetheless, more pharmacokinetic and pharmacodynamic studies are needed to fully understand this schedule-dependence phenomenon. PMID:24860238

Venipuncture and intravenous infusion access during zero-gravity flight

NASA Technical Reports Server (NTRS)

Krupa, Debra T.; Gosbee, John; Billica, Roger; Bechtle, Perry; Creager, Gerald J.; Boyce, Joey B.

1991-01-01

The purpose of this experiment is to establish the difficulty associated with securing an intravenous (IV) catheter in place in microgravity flight and the techniques applicable in training the Crew Medical Officer (CMO) for Space Station Freedom, as well as aiding in the selection of appropriate hardware and supplies for the Health Maintenance Facility (HMF). The objectives are the following: (1) to determine the difficulties associated with venipuncture in a microgravity environment; (2) to evaluate the various methods of securing an IV catheter and attached tubing for infusion with regard to the unique environment; (3) to evaluate the various materials available for securing an intravenous catheter in place; and (4) to evaluate the fluid therapy administration system when functioning in a complete system. The inflight test procedures and other aspects of the KC-135 parabolic flight test to simulate microgravity are presented.

Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

PubMed

Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

2014-07-01

Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

Intravenous thiamine is associated with increased oxygen consumption in critically ill patients with preserved cardiac index.

PubMed

Berg, Katherine M; Gautam, Shiva; Salciccioli, Justin D; Giberson, Tyler; Saindon, Brian; Donnino, Michael W

2014-12-01

Oxygen consumption may be impaired in critically ill patients. To evaluate the effect of intravenous thiamine on oxygen consumption ([Formula: see text]o2) in critically ill patients. This was a small, exploratory open-label pilot study conducted in the intensive care units at a tertiary care medical center. Critically ill adults requiring mechanical ventilation were screened for enrollment. Oxygen consumption ([Formula: see text]o2) and cardiac index (CI) were recorded continuously for 9 hours. After 3 hours of baseline data collection, 200 mg of intravenous thiamine was administered. The outcome was change in [Formula: see text]o2 after thiamine administration. Twenty patients were enrolled and 3 were excluded because of incomplete [Formula: see text]o2 data, leaving 17 patients for analysis. There was a trend toward increase in [Formula: see text]o2 after thiamine administration (16.3 ml/min, SE 8.5; P = 0.052). After preplanned adjustment for changes in CI in case of a delivery-dependent state in some patients (with exclusion of one additional patient because of missing CI data), this became statistically significant (16.9 ml/min, SE 8.6; P = 0.047). In patients with average CI greater than our cohort's mean value of 3 L/min/m(2), [Formula: see text]o2 increased by 70.9 ml/min (±16; P < 0.0001) after thiamine. Thiamine had no effect in patients with reduced CI (< 2.4 L/min/m(2)). There was no association between initial thiamine level and change in [Formula: see text]o2 after thiamine administration. The administration of a single dose of thiamine was associated with a trend toward increase in [Formula: see text]o2 in critically ill patients. There was a significant increase in [Formula: see text]o2 in those patients with preserved or elevated CI. Further study is needed to better characterize the role of thiamine in oxygen extraction. Clinical trial registered with www.clinicaltrials.gov (NCT01462279).

Pharmacokinetics of Intravenous Sildenafil in Children with Palliated Single Ventricle Heart Defects: Effect of Elevated Hepatic Pressures

PubMed Central

Hill, Kevin D.; Sampson, Mario R.; Li, Jennifer S.; Tunks, Robert D.; Schulman, Scott R.; Cohen-Wolkowiez, Michael

2015-01-01

Aims Sildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects. Methods A population pharmacokinetic model was developed using data from 20 single ventricle children receiving single dose intravenous sildenafil during cardiac catheterization. Nonlinear mixed effect modeling was used for model development and covariate effects were evaluated based on estimated precision and clinical significance. Results The analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance = 0.62 L/H/kg); however, clearance of des-methyl-sildenafil (1.94 × (hepatic pressure/9)−1.33 L/h/kg) was predicted to decrease ~7 fold as hepatic pressure increased from 4 to 18 mm Hg. Predicted drug exposure was increased by ~1.5 fold in subjects with hepatic pressures ≥ 10 mm Hg versus < 10 mm Hg (median area under the curve = 533 μg*h/L versus 792 μg*h/L). Discussion Elevated hepatic pressure delays clearance of the sildenafil metabolite, des-methyl-sildenafil and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessment in patients with unique cardiovascular physiology that may affect drug metabolism. PMID:26197839

Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats.

PubMed

Kock, M; Thompson, E; Vulliet, P R; Brooks, D L

1994-10-01

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

Pharmacodynamic effects and relationships to plasma and oral fluid pharmacokinetics after intravenous cocaine administration.

PubMed

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

2016-06-01

No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations. Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry. Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing. OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals. Copyright © 2016. Published by Elsevier Ireland Ltd.

Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel

PubMed Central

Dickson, Price E.; Miller, Mellessa M.; Calton, Michele A.; Bubier, Jason A.; Cook, Melloni N.; Goldowitz, Daniel; Chesler, Elissa J.; Mittleman, Guy

2015-01-01

Rationale Cocaine addiction is a major public health problem with a substantial genetic basis for which the biological mechanisms remain largely unknown. Systems genetics is a powerful method for discovering novel mechanisms underlying complex traits, and intravenous drug self-administration (IVSA) is the gold standard for assessing volitional drug use in preclinical studies. We have integrated these approaches to identify novel genes and networks underling cocaine use in mice. Methods Mice from 39 BXD strains acquired cocaine IVSA (0.56 mg/kg/infusion). Mice from 29 BXD strains completed a full dose-response curve (0.032 – 1.8 mg/kg/infusion). Results We identified independent genetic correlations between cocaine IVSA and measures of environmental exploration and cocaine sensitization. We identified genome-wide significant QTL on chromosomes 7 and 11 associated with shifts in the dose-response curve and on chromosome 16 associated with sessions to acquire cocaine IVSA. Using publicly available gene expression data from the nucleus accumbens, midbrain, and prefrontal cortex of drug-naïve mice, we identified Aplp1 and Cyfip2 as positional candidates underlying the behavioral QTL on chromosomes 7 and 11, respectively. A genome-wide significant trans-eQTL linking Fam53b (a GWAS candidate for human cocaine dependence) on chromosome 7 to the cocaine IVSA behavioral QTL on chromosome 11 was identified in the midbrain; Fam53b and Cyfip2 were co-expressed genome-wide significantly in the midbrain. This finding indicates that cocaine IVSA studies using mice can identify genes involved in human cocaine use. Conclusions These data provide novel candidate genes underlying cocaine IVSA in mice, and suggest mechanisms driving human cocaine use. PMID:26581503

Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

PubMed Central

Davies, B E; Boon, R; Horton, R; Reubi, F C; Descoeudres, C E

1988-01-01

1. Serum concentrations of amoxycillin and clavulanic acid were measured in patients with end-stage renal disease (ESRD) following intravenous administration of 1.2 g Augmentin. Augmentin was administered on a non-dialysis day and 2 h prior to a 4 h dialysis session. 2. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for amoxycillin on the non-dialysis day were 14.4 ml min-1, 19.2 h, 14.9 l and 13.6 h, respectively. 3. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for amoxycillin were 77.1 ml min-1, 91.5 ml min-1, 0.64 and 2.30 h, respectively. 4. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for clavulanic acid on the non-dialysis day were 43.6 ml min-1, 4.4 h, 11.0 l and 3.05 h, respectively. 5. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for clavulanic acid were 92.8 ml min-1, 136 ml min-1, 0.65 and 1.19 h, respectively. 6. The total serum clearance on the non-dialysis day, which represents non-renal clearance, was lower than that in normal subjects for both amoxycillin and clavulanic acid. These data would suggest some degree of hepatic impairment in patients with ESRD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3190988

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial.

PubMed

Sng, Ban Leong; Du, Wei; Lee, Man Xin; Ithnin, Farida; Mathur, Deepak; Leong, Wan Ling; Sultana, Rehena; Han, Nian-Lin R; Sia, Alex Tiong Heng

2018-05-01

Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. A randomised, double-blind controlled trial. Single-centre, KK Women's and Children's Hospital, Singapore. Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive hypertension or the total vasopressor requirement. The DIVA group had less wobble in system performance. Maternal and neonatal outcomes were similar. The DIVA system achieved better control of maternal blood pressure after spinal anaesthesia than manual vasopressor bolus administration. Clinicaltrials.gov identifier: NCT02277730.

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.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

PubMed Central

Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Pharmacokinetic investigations in adult humans after parenteral administration of the lysine salt of acetyl-salicylic acid.

PubMed

von Voss, H; Göbel, U; Petrich, C; Pütter, J

1978-11-15

The lysine salt of acetylsalicylic acid was administered intravenously to four volunteers and intramuscularly to three of them. The drug was tolerated without any observed side effects. Immediately after intravenous application most of the plasma salicylate was acetylsalicylic acid. The highest concentration of acetylsalicylic acid was found after 2 minutes, highest levels of salicylic acid after 60 minutes. Elimination of acetylsalicylic acid was relatively quick within the first period after intravenous administration according to a half-life of 8 minutes. Half-life of salicylic acid was determined to be 3 hours. Intramuscular application results in a constant blood level for a longer period. Bioavailability of acetylsalicylic acid was slightly lower after intramuscular application than after intravenous administration.

Ceruletide intravenous dose-response study by a simplified scintigraphic technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.

1985-04-01

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg andmore » larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.« less

[Intravenous rehydration for diarrheal dehydration of eutrophic children: survey of protocols provided at Colombian medical schools].

PubMed

Flórez, Iván Darío; Ramos, Esteban; Bernal, Carlos; Cuéllar, Olga Juliana; Cornejo, José William

2011-01-01

In all cases of severe dehydration from diarrhea, WHO recommends rapid rehydration. If oral rehydration in children is contraindicated, intravenous rehydration is recommended for immediate administration. However, methods of intravenous rehydration appear to be inadequately addressed in the medical schools of Colombia. Current approaches to oral rehydration were summarized, and instructors were informed concerning current WHO recommendations. A survey was designed for pediatric instructors in Colombian medical schools. Direct questions about rehydration methods were included as well as presentation of theoretical clinical situations with dehydrated children. The survey also asked for the conditions necessary for intravenous rehydration and method of administration (volume, solution, concentration and speed of infusion). Forty-one surveys were included (82% of medical schools in Colombia). Inadequate contraindications for oral rehydration therapy were made in 41%. Rapid and slow intravenous rehydration was recommended in 71% and 29%, respectively; 57% recommended fluid bolus to rehydrate. Adequate volumes were recommended by less than half of the respondents and adequate sodium concentration was recommended by 85%. In 56% of medical schools, glucose was not included in solutions and 66% use Ringer lactate. Normal saline solution, dextrose solution with electrolytes and polyelectrolytes solutions are also used. Misconceptions are common concerning the contraindications to oral rehydration therapy. One-third of medical schools promote a slow therapy despite the superiority of the rapid therapy. Uniformity for rapid therapy schemes is lacking. Bolus rehydration is commonly advocated despite the fact that this method is unsupported by the literature. Concepts about rehydration must be updated in medical schools and a national guide for intravenous rehydration is recommended.

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

PubMed

Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

2014-04-01

To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

Construct validity and reliability of the Single Checking Administration of Medications Scale.

PubMed

O'Connell, Beverly; Hawkins, Mary; Ockerby, Cherene

2013-06-01

Research indicates that single checking of medications is as safe as double checking; however, many nurses are averse to independently checking medications. To assist with the introduction and use of single checking, a measure of nurses' attitudes, the thirteen-item Single Checking Administration of Medications Scale (SCAMS) was developed. We examined the psychometric properties of the SCAMS. Secondary analyses were conducted on data collected from 503 nurses across a large Australian health-care service. Analyses using exploratory and confirmatory factor analyses supported by structural equation modelling resulted in a valid twelve-item SCAMS containing two reliable subscales, the nine-item Attitudes towards single checking and three-item Advantages of single checking subscales. The SCAMS is recommended as a valid and reliable measure for monitoring nurses' attitudes to single checking prior to introducing single checking medications and after its implementation. © 2013 Wiley Publishing Asia Pty Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov; Johnson, Jerry D.; Hong, S. Peter

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 followingmore » 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. • �

Intravenous infusion of PAF affects ovulation, fertilization and preimplantation embryonic development in NZB x NZW F1 hybrid mice.

PubMed

Sakellariou, Maria; Drakakis, Peter; Antonopoulou, Smaragdi; Anagnostou, Elli; Loutradis, Dimitris; Patargias, Theoxaris

2008-03-01

Platelet Activating Factor (PAF) is a bioactive phospholipid, which exhibits a variety of biological activities and plays a significant role in all aspects of reproduction. In this work, a single intravenous injection of various concentrations of PAF shortly after Human Chorionic Gonadotropin (HCG) administration as well as 24 and 48 h before HCG administration was studied in NZB x NZW F1 hybrid mice. Optimum results were observed when PAF was injected just after the administration of HCG. In this protocol, the concentrations of PAF exhibited bell-shaped response to every stage of development. Any concentration of PAF between 5.5 x 10(-11) and 5.5 x 10(-15)g/g b.w., caused an improved ovulation rate, an increased fertilization rate, an increased rate of cell cycle and an enhanced hatching blastocyst rate (P<0.05 for all stages). Injection of lyso-PAF had no effect in any stage. Our data show that the effect of PAF on early stages of embryo development in vitro is dependent on its way of administration, on the concentrations used as well as on the time PAF is injected.

[Complications due to contrast agent administration: what has been confirmed in prevention?].

PubMed

Schönenberger, E; Mühler, M; Dewey, M

2010-12-01

Computed tomography (CT) and magnetic resonance imaging (MRI) have been evaluated by internists to be the most important medical innovations. Often, intravenous contrast agent administration is required for answering the clinical questions to CT and MRI. In this review we present an overview of the most common and most important aspects that need to be considered prior to intravenous contrast agent administration. We discuss aspects of renal impairment (contrast-induced nephropathy, nephrogenic systemic fibrosis), allergy-like reactions, hyperthyroidism, and pregnancy and breast-feeding.

Sedative-analgesic agent administration in children: analysis of use and complications in the emergency department.

PubMed

Woolard, D J; Terndrup, T E

1994-01-01

The frequency of, indications for, and complications from non-acetaminophen sedative-analgesic agents (SAAs) administered to children less than 16 years of age in the emergency department (ED) were determined by a retrospective review. All 21,353 charts from a single university hospital ED over a 16-month period were included. Few children (N = 759; 3.5%) received SAAs. Of 919 total doses, 13% of children received a second and 4.5% received a third SAA. The group was 59% male. Most children were < or = 10 years of age. Sixty-two percent of SAAs were either sedatives or opioids. Sedatives given included chloral hydrate, diazepam, lorazepam, midazolam, and phenobarbital. Opioids given included morphine, codeine, and meperidine. Indications for SAAs included painful procedures, analgesia, radiographic imaging, and seizure activity. Complications (N = 51; 6.7%) included inadequate sedation, vomiting, and respiratory depression or oxygen desaturation. Respiratory depression or oxygen desaturation occurred only after intravenous administration of SAAs for seizures. In children, non-acetaminophen SAAs are used most commonly in younger patients requiring sedation for painful procedures or for radiologic imaging. Respiratory depression was observed only after intravenous administration of anticonvulsants.

Hypotensive Effect and Accumulation of Dinitrosyl Iron Complexes in Blood and Tissues after Intravenous and Subcutaneous Injection.

PubMed

Timoshin, A A; Lakomkin, V L; Abramov, A A; Ruuge, E K; Vanin, A F

2016-12-01

Subcutaneous injection of Oxacom with glutathione-bound dinitrosyl iron complex as the active principle produced a slower drop of mean BP and longer accumulation of protein-bound dinitrosyl iron complexes in whole blood and tissues than intravenous injection of this drug, while durations of hypotensive effect in both cases were practically identical. In contrast to intravenous injection of the drug, its subcutaneous administration was not characterized by a high concentration of protein-bound dinitrosyl iron complexes in the blood at the onset of experiment; in addition, accumulation of these NO forms in the lungs was more pronounced after subcutaneous injection than after intravenous one.

Preincisional administration of intravenous or subcutaneous infiltration of low-dose ketamine suppresses postoperative pain after appendectomy

PubMed Central

Honarmand, Azim; Safavi, Mohammadreza; Karaky, Hasan

2012-01-01

Background Ketamine, an N-methyl-D-aspartate receptor antagonist, can suppress hyperalgesia and allodynia. The purpose of the present study was to evaluate the clinical efficacy of preincisional intravenous or subcutaneous infiltration of ketamine for postoperative pain relief after appendectomy. Methods Ninety patients, aged 18–60 years, scheduled for appendectomy was enrolled in this study. Patients were divided into three groups of 30 each and received subcutaneous infiltration of ketamine 0.5 mg/kg (KS), intravenous ketamine 0.5 mg/kg (KI), or subcutaneous infiltration of normal saline 3 mL (C) before surgery. Visual analog scale (VAS) values and analgesic consumption were evaluated for 24 hours after surgery. Results VAS scores were significantly lower at the time of arrival in the recovery room, and at 10, 20, and 30 minutes thereafter in group KI and group KS compared with group C (P < 0.05). VAS scores were not significantly different between group KI and group KS at these intervals. Postoperative VAS scores were significantly lower at 6, 12, 18, and 24 hours in group KI compared with group C (P < 0.05). In group KS, the postoperative VAS score was significantly lower at 6 hours (P < 0.05). VAS scores were significantly lower at 12, 18, and 24 hours after surgery in group KI compared with group KS (P < 0.05). Conclusion A 0.5 mg/kg dose of ketamine given at approximately 15 minutes before surgery by the intravenous route provided analgesia for 24 hours after surgery in patients undergoing appendectomy. PMID:22328829

Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study.

PubMed

Poddar, Karan; Sharma, Rohan; Ng, Yu-Tze

2016-08-01

Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus. Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide. Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient. In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study.

PubMed

Lerner, Michael Z; Matsushita, Takashi; Lankford, Karen L; Radtke, Christine; Kocsis, Jeffery D; Young, Nwanmegha O

2014-11-01

Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Animal Research. Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

PubMed

Orito, Kensuke; Kawarai-Shimamura, Asako; Ogawa, Atsushi; Nakamura, Atsushi

2017-12-22

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

[Observational study of outpatient unit duration of stay depending on the route of administration (intravenous vs subcutaneous) for a targeted therapy].

PubMed

Despiau, Frédéric; Zagala, Yann; Delord, Jean-Pierre; Montastruc, Marion; Lacaze, Jean-Louis; Ferrand, Régis; Bombail, Marie

2017-10-01

New routes of administration available for some targeted therapies, especially subcutaneous injections, have an impact not only on the patients' daycare experience, but also on the unit's organization. This observational study conducted on 48 voluntary patients at the Institut universitaire du cancer Toulouse-Oncopole shows that the mean duration of the outpatient unit stay is diminished by one hour when a subcutaneous injection is used instead of an intravenous route. This duration decrease is mainly caused by an 82% average reduction in treatment duration. However, the waiting times before and after the treatment itself are not significantly impacted. Organizational methods related to the treatment prescription and preparation remain indeed the same. Anticipated prescription is not noticeably impacted either. This reduction of the duration of stay will truly be obtained if the whole unit's organization is adapted. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

A needle-free reconstitution and transfer system for compounded sterile intravenous drug solutions in compliance with United States Pharmacopeia Chapter <797> standards.

PubMed

Marks, Zach

2014-01-01

Today's health-system pharmacists and those in independent practice face risks, including exposure to potent cytotoxic drugs via needlesticks, that are associated with preparing intravenous compounded sterile preparations for immediate use. Healthcare givers who administer such medications also risk exposure to needlesticks. Those hazards can be minimized when the pharmacist thoroughly understands and complies with current standard operating procedures for preparing intravenous compounded sterile preparations and the healthcare giver uses a needle-free system for drug reconstitution and administration. The components of an overall needlestick risk-reduction strategy to ensure safety in the preparation (and eventual administration) of intravenous compounded sterile preparations should therefore include the use of needle-free connection and administration devices as well as hand-hygiene training, aseptic technique competency evaluation and training, and the maximum use of commercially available or ready-to-use dosage forms. This article, which focuses on the pharmacist's use of a needle-free reconstitution and transfer system for compounded sterile intravenous drug solutions, uses as an example the Vial2Bag (Medimop Medical Projects, Ltd., [a subsidiary of West Pharmaceutical Services, Inc., Exton, Pennsylvania], Ra'anana, Israel), which complies with United States Pharmacopeia Chapter <797> standards. Features of that system are summarized for easy reference.

Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radziuk, J.

1989-08-01

The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or (3-{sup 3}H)glucose and a marker for gluconeogenesis, (U-{sup 14}C)lactate or sodium ({sup 14}C)bicarbonate ({sup 14}C)bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ((6-{sup 3}H)glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of ({sup 14}C)glucose production or for dilution of {sup 14}C with citric acid cycle carbon in the oxaloacetatemore » pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from (U-{sup 14}C)-lactate incorporation and 7.4 +/- 1.3 g calculated using ({sup 14}C)bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for (U-{sup 14}C)lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with ({sup 14}C)bicarbonate as tracer (P less than 0.05, vs. ({sup 14}C)-lactate as tracer). When (2-{sup 14}C)acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that {sup 14}CO{sub 2} is a potentially useful marker for the gluconeogenetic process in vivo.« less

PM101: a cyclodextrin-based intravenous formulation of amiodarone devoid of adverse hemodynamic effects.

PubMed

Cushing, Daniel J; Kowey, Peter R; Cooper, Warren D; Massey, Bill W; Gralinski, Michael R; Lipicky, Raymond J

2009-04-01

Intravenous amiodarone (Amiodarone i.v.) is widely used to treat cardiac arrhythmias. The most frequent clinical adverse event associated with Amiodarone i.v. administration is systemic hypotension which has been attributed to the cosolvents used in the formulation, polysorbate 80 and benzyl alcohol. To minimize hypotension Amiodarone i.v. is diluted in 5% dextrose in water prior to administration and slowly infused. PM101 is a novel intravenous formulation that uses sulfobutylether-7-beta-cyclodextrin to solubilize amiodarone, and thus should be devoid of the untoward hemodynamic effects associated with polysorbate 80 and benzyl alcohol. Beagle dogs (n=7/group) were anesthetized with morphine and alpha-chloralose and instrumented to assess aortic blood pressure, cardiac output, cardiac contractility, and heart rate. Animals were treated with the U.S. approved human-equivalent loading dose (2.14 mg/kg) of Amiodarone i.v., PM101, and their respective vehicle controls. Administration of Amiodarone i.v. rapidly and significantly decreased mean aortic pressure, cardiac output, and cardiac contractility. A significant increase in heart rate was also observed as was a transient, but not significant, decrease in systemic vascular resistance. A similar pattern of rapid and significant hemodynamic changes was produced by the Amiodarone i.v. Vehicle (polysorbate 80/benzyl alcohol) alone. In marked contrast, PM101 and its vehicle produced no significant hemodynamic effects. This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.

[18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia.

PubMed

Tan, Chengbo; Zhao, Songji; Higashikawa, Kei; Wang, Zifeng; Kawabori, Masahito; Abumiya, Takeo; Nakayama, Naoki; Kazumata, Ken; Ukon, Naoyuki; Yasui, Hironobu; Tamaki, Nagara; Kuge, Yuji; Shichinohe, Hideo; Houkin, Kiyohiro

2018-05-02

The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [ 18 F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [ 18 F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [ 18 F]DPA-714 PET was performed 3 and 10 days after MCAO. Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [ 18 F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group. The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [ 18 F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

Formulation and Evaluation of Irinotecan Suppository for Rectal Administration

PubMed Central

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0–30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0–30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability. PMID:24596626

Formulation and evaluation of irinotecan suppository for rectal administration.

PubMed

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0-30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0-30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability.

Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

PubMed

Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

2018-05-16

Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

Single-dose toxicokinetics of permethrin in broiler chickens.

PubMed

Gögebakan, T; Eraslan, G

2015-01-01

Single-dose toxicokinetics of permethrin was investigated in broiler chickens. A total of 20 male broiler chickens were assigned at random to two groups of 10 at 30 days of age. A single dose of 10 mg/kg body weight of permethrin was administered intravenously to the first group; in the second group, the same dose was administered into the crop. Serum permethrin was measured using an electron capture detector and gas chromatography equipment. The derived serum permethrin concentration/time curve demonstrated that the distribution kinetics of permethrin was well described by a two-compartment open model. For intravenous permethrin administration, the half-life at λ phase (t1/2λ), mean residence time (MRT) and area under the concentration-time curve in 0→∞ (AUC0→∞) values respectively were 4.73 ± 1.00 h, 5.06 ± 1.05 h and 16.45 ± 3.28 mg/h/l. In contrast, the Cmax, tmax, t1/2λ, MRT and AUC0→∞ values respectively of the group given intra-crop permethrin were 0.60 ± 0.42 μg/ml, 0.55 ± 0.19 h, 5.54 ± 0.78 h, 7.06 ± 0.63 h and 1.95 ± 0.97 mg/h/l. The bioavailability of permethrin was 0.11. For both administration routes, the residence time of permethrin in the body was short and the bioavailability of permethrin was low. These results are relevant for assessing the use and safety of permethrin.

Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke

PubMed Central

Broderick, Joseph P.; Palesch, Yuko Y.; Demchuk, Andrew M.; Yeatts, Sharon D.; Khatri, Pooja; Hill, Michael D.; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; Silver, Frank L.; von Kummer, Rüdiger; Molina, Carlos A.; Demaerschalk, Bart M.; Budzik, Ronald; Clark, Wayne M.; Zaidat, Osama O.; Malisch, Tim W.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Martin, Renée H.; Foster, Lydia D.; Tomsick, Thomas A.

2013-01-01

BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with

Pharmacokinetics of intravenous tramadol in dogs

PubMed Central

McMillan, Chantal J.; Livingston, Alex; Clark, Chris R.; Dowling, Patricia M.; Taylor, Susan M.; Duke, Tanya; Terlinden, Rolf

2008-01-01

The purpose of this study was to determine the pharmacokinetics of tramadol and the active metabolite mono-O-desmethyltramadol (M1) in 6 healthy male mixed breed dogs following intravenous injection of tramadol at 3 different dose levels. Verification of the metabolism to the active metabolite M1, to which most of the analgesic activity of this agent is attributed to, was a primary goal. Quantification of the parent compound and the M1 metabolite was performed using gas chromatography. Pharmacodynamic evaluations were performed at the time of patient sampling and included assessment of sedation, and evaluation for depression of heart and respiratory rates. This study confirmed that while these dogs were able to produce the active M1 metabolite following intravenous administration of tramadol, the M1 concentrations were lower than previously reported in research beagles. Adverse effects were minimal, with mild dose-related sedation in all dogs and nausea in 1 dog. Analgesia was not documented with the method of assessment used in this study. Tramadol may be useful in canine patients, but additional studies in the canine population are required to more accurately determine the effective clinical use of the drug in dogs and quantification of M1 concentrations in a wider population of patients. PMID:18783021

Pharmacokinetics of tilmicosin in beef cattle following intravenous and subcutaneous administration.

PubMed

Lombardi, K R; Portillo, T; Hassfurther, R; Hunter, R P

2011-12-01

The intravenous pharmacokinetic profile of tilmicosin is yet to be achieved because of the cardiovascular effects of tilmicosin. This study summarizes two pharmacokinetic studies that provided complete pharmacokinetic profile of tilmicosin in cattle. The first study was a pharmacokinetic study of tilmicosin in beef calves dosed by i.v. infusion over 5 h. The second study was a subcutaneous (s.c.) pharmacokinetic study comparing the pharmacokinetic profile of tilmicosin in light (approximately 170 kg) and heavy (approximately 335 kg) beef cattle and comparing the labeled dose range of 10 or 20 mg/kg dose. The data from the two different studies were used to calculate bioavailability values, which support the assumption that tilmicosin is 100% bioavailable in cattle. The results from the second study showed that the weight of an animal when administered tilmicosin does not have a significant effect on exposure, but did demonstrate that doubling the dose of tilmicosin administered doubles the systemic exposure to tilmicosin. © 2011 Blackwell Publishing Ltd.

Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department.

PubMed

Rudis, Maria I; Touchette, Daniel R; Swadron, Stuart P; Chiu, Amy P; Orlinsky, Michael

2004-03-01

Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse

[Erythropoiesis-stimulating agents in chronic kidney disease: which route of administration?].

PubMed

Borrelli, S; Baldanza, D; Scigliano, R; Catapano, F; Grimaldi, M; Calabria, M; Zamboli, P; Minutolo, R; De Nicola, L; Conte, G

2009-01-01

In the last twenty years, erythropoiesis-stimulating agents (ESAs) have improved the management of renal anemia, with significant amelioration of quality of life in patients on hemodialysis. ESAs can be administered both intravenously and subcutaneously. In predialysis chronic kidney disease and in peritoneal dialysis, the administration route is necessarily subcutaneous. In hemodialysis the intravenous route was initially preferred because of the presence of ready vascular access for drug administration. Subsequent studies have demonstrated that the subcutaneous route allowed the achievement of optimal levels of hemoglobin with a reduction of mean administered dose, number of injections, and costs. A few years ago, the finding of a higher risk of pure red cell aplasia associated with subcutaneous administration of epoetin reopened the debate about the route of administration. We here review the studies on the preferable route of administration of epoetin and darbepoetin- alpha, in terms of efficacy and safety, and take a look at future perspectives.

Home intravenous therapy: Part I--Issues.

PubMed

McAbee, R R; Grupp, K; Horn, B

1991-01-01

Concerns related to providing home intravenous therapy were among the top ten clinical problems identified by Northwest Medicare-certified home care agencies in a 1986 survey. This paper addresses issues related to home intravenous therapy and provides lists of resources for the development of home intravenous therapy programs. Part I of the paper covers concerns related to intravenous therapy as expressed by home care agencies in the Northwest and synthesized the literature about home intravenous therapies. Survey results are presented, followed by a discussion of client and caregiver concerns. These include: discharge planning, client admission criteria and client and caregiver education. Standards, staffing, and staff education issues are discussed followed by sections on economics, marketing regulations and legal and ethical concerns. Finally, there is a discussion of issues related to specific types of intravenous therapies: parenteral nutrition, antibiotic therapy; chemotherapy; blood and blood component therapy and other less frequently used types of intravenous therapies. Each therapy is discussed with regard to complications, client and caregiver instruction and financial considerations. Part II of the paper is a resource guide which lists resources that agencies may use to develop a home intravenous therapy program. In the first section, national organizations and journals and books concerned with intravenous therapy are listed as well as journal articles, guidelines and guidebooks and client and provider educational materials. National and regional product and service representatives of intravenous therapy related companies are also listed. In the second section, addresses for the State Boards of Nursing are given for Alaska, Idaho, Montana, Oregon and Washington. Each state section includes a list of those agencies who indicated in the 1988 survey that they would be willing to share materials. In addition, product and service vendors of intravenous

The prehospital intravenous access assessment: a prospective study on intravenous access failure and access delay in prehospital emergency medicine.

PubMed

Prottengeier, Johannes; Albermann, Matthias; Heinrich, Sebastian; Birkholz, Torsten; Gall, Christine; Schmidt, Joachim

2016-12-01

Intravenous access in prehospital emergency care allows for early administration of medication and extended measures such as anaesthesia. Cannulation may, however, be difficult, and failure and resulting delay in treatment and transport may have negative effects on the patient. Therefore, our study aims to perform a concise assessment of the difficulties of prehospital venous cannulation. We analysed 23 candidate predictor variables on peripheral venous cannulations in terms of cannulation failure and exceedance of a 2 min time threshold. Multivariate logistic regression models were fitted for variables of predictive value (P<0.25) and evaluated by the area under the curve (AUC>0.6) of their respective receiver operating characteristic curve. A total of 762 intravenous cannulations were enroled. In all, 22% of punctures failed on the first attempt and 13% of punctures exceeded 2 min. Model selection yielded a three-factor model (vein visibility without tourniquet, vein palpability with tourniquet and insufficient ambient lighting) of fair accuracy for the prediction of puncture failure (AUC=0.76) and a structurally congruent model of four factors (failure model factors plus vein visibility with tourniquet) for the exceedance of the 2 min threshold (AUC=0.80). Our study offers a simple assessment to identify cases of difficult intravenous access in prehospital emergency care. Of the numerous factors subjectively perceived as possibly exerting influences on cannulation, only the universal - not exclusive to emergency care - factors of lighting, vein visibility and palpability proved to be valid predictors of cannulation failure and exceedance of a 2 min threshold.

A randomized controlled trial of preprocedure administration of parecoxib for therapeutic endoscopic retrograde cholangiopancreatography.

PubMed

Amornyotin, Somchai; Chalayonnawin, Wiyada; Kongphlay, Siriporn

2012-01-01

Parecoxib is occasionally used for analgesia in postprocedural patients. The clinical efficacy of parecoxib used for endoscopic retrograde cholangiopancreatography (ERCP) is controversial. The aim of the study was to determine the clinical efficacy of preprocedure administration of parecoxib for therapeutic ERCP patients. Eighty-five patients who underwent therapeutic ERCP in a single year were randomly assigned to normal saline group (C, n = 43) and parecoxib group (P, n = 42). Patients in group C received normal saline and those in group P received 40 mg of parecoxib intravenously in equivalent volume. Patients in both groups received the saline or parecoxib 60 seconds before administration of the sedative agents. All patients were monitored for the depth of sedation by using the Narcotrend(TM) monitor, maintaining stage D0-E0 during ERCP. All patients were oxygenated with 100% O(2) via nasal cannula and sedated with 0.03 mg/kg of intravenous midazolam and 1 μg/kg of intravenous fentanyl as well as the titration of intravenous propofol. After the ERCP procedure, pethidine in an intramuscular dose of 0.5-1.0 mg/kg was used as rescue medication. The pain scores (visual analog scale [VAS], 0-10) at 2, 12, and 24 hours post-ERCP, the total number of doses of pethidine used, the dose volume of pethidine used, patient satisfaction, endoscopist satisfaction, and complications were recorded. There were no significant differences in sedative and analgesic agents used during the procedure, pain at 24 hours post-ERCP, endoscopist satisfaction, and complications in both groups. The total number of doses of pethidine used post-ERCP in group C was significantly higher than in group P. Additionally, the mean pain score at 2 and 12 hours post-ERCP in group C was significantly greater than in group P. Patient satisfaction in group P was higher than in group C. Preprocedure administration of parecoxib for therapeutic ERCP patients was clinically effective. The analgesic efficacy

[Skin necrosis resulting from the extravasation of intravenous injections].

PubMed

Ikhefoulma, Soumaya; Mahiou, Abelhamid; Perillat, Isabelle

2012-09-01

Extravasation is the diffusion of a product injected intravenously into the perivascular or subcutaneous spaces. Skin necrosis of iatrogenic origin can be observed for example with a subcutaneous perfusion of solution containing potassium chloride or the extravasation of 30% hypertonic glucose serum. Whenever a product is injected, the administration route for which the product has obtained marketing authorisation must be respected and a perfusion time of at least 4 to 5 hours per litre of solution perfused must be observed.

Inversion-based propofol dosing for intravenous induction of hypnosis

NASA Astrophysics Data System (ADS)

Padula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.

2016-10-01

In this paper we propose an inversion-based methodology for the computation of a feedforward action for the propofol intravenous administration during the induction of hypnosis in general anesthesia. In particular, the typical initial bolus is substituted with a command signal that is obtained by predefining a desired output and by applying an input-output inversion procedure. The robustness of the method has been tested by considering a set of patients with different model parameters, which is representative of a large population.

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances

PubMed Central

ORITO, Kensuke; KAWARAI-SHIMAMURA, Asako; OGAWA, Atsushi; NAKAMURA, Atsushi

2017-01-01

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20–50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25–50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26–370 sec), median duration of emesis was 151.5 sec (range, 30–780 sec), and median number of emesis episodes was 2 (range, 1–8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting. PMID:29093310

Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion.

PubMed

Muñoz, M; Breymann, C; García-Erce, J A; Gómez-Ramírez, S; Comin, J; Bisbe, E

2008-04-01

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation-induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side-effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings.

Pharmacokinetics of theophylline after administration of suppositories formulation.

PubMed

Abou-Basha, L I; Wahman, L F; Hamza, A; Aboul-Enein, Hassan Y

2005-01-01

Asthma is a public health problem for developed countries. It attacks all age groups but often starts in childhood. Theophylline ethanoate of piperazine in a suppository form is one of the treatments of asthmatic children. The pharmacokinetics of theophylline were evaluated in 24 healthy male subjects after administration of theophylline ethanoate of piperazine suppositories (PR) (Minophylline 500 mg. Alexandria Co.) and single injection intravenous (IV) of theophylline ethanoate of piperazine (Minophylline ampoules 500 mg Alexandria Co.). The theophylline serum levels were determined by an ELISA method. Peak theophylline plasma concentration, Cmax, (mean +/- S.D) was 21.5 +/- 2.10 microg/mL & 14 +/- 0.90 microg/mL; AUC(0-t), values were 80.9 and 67. 4 microg x ml x hr for the reference IV preparation and suppositories, respectively. The median peak time, Tmax, was 0.5 hr for theophylline rectal administration. The above mentioned results demonstrate the possibilities of using theophylline (Minophylline Suppositories--500 mg Alexandria Co.) in asthmatic children in rural and desert areas away from health care personnel.

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study

PubMed Central

Churilov, Leonid

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting. PMID:29659631

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study.

PubMed

Chiam, Elizabeth; Bellomo, Rinaldo; Churilov, Leonid; Weinberg, Laurence

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.

76 FR 67192 - Administration on Children, Youth and Families Announces the Award of Five Single-Source...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Administration on Children, Youth and Families Announces the Award of Five Single-Source Expansion Supplement Grants To Support Expanded Technical Assistance Activities in the Field of Child Welfare AGENCY: Children's Bureau...

Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities.

PubMed

Ibrahim, Nehal; Ibrahim, Hany; Sabater, Alicia Moreno; Mazier, Dominique; Valentin, Alexis; Nepveu, Françoise

2015-11-30

More than 40 years after its discovery, artemisinin has become the most promising antimalarial agent. However, no intravenous formulation is available due to its poor aqueous solubility. Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. The nanoparticles were prepared by a combination of a bottom-up and a top-down processes and characterized by different spectroscopic techniques. The preparation process was optimized to develop a nanoformulation with the smallest possible diameter and good homogeneity suitable for intravenous injection enabling direct contact of artemisinin with infected erythrocytes. Chemically and physically stable artemisinin nanoparticles were obtained with excellent entrapment efficiency. In in vitro experiments, the artemisinin nanoformulation was interestingly more effective than non-formulated artemisinin. In Plasmodiumm falciparum-infected 'humanized' mice, the nanoparticles proved to be highly effective with 96% parasitemia inhibition at 10mg/kg/day, prolonging mean survival time without recrudescence. This nanoparticulate albumin-bound system allows the intravenous administration of artemisinin for the first time without harsh organic solvents or cosolvents with 100% bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

PubMed

Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

2016-01-01

A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

Humoral anti-OV-TL 3 response after the intravenous administration of radiolabelled Fab' or F(ab')2 fragments in ovarian cancer patients.

PubMed

Tibben, J G; Thomas, C M; Massuger, L F; Segers, M F; Schijf, C P; Corstens, F H; Boerman, O C

1995-10-01

The human anti-mouse antibody (HAMA) response was determined in the serum of patients suspected of having ovarian cancer who underwent radioimmunoscintigraphy with either 99Tcm-OV-TL 3 Fab' (n = 20) or 111In-DTPA-OV-TL 3 F(ab')2 (n = 73). Blood samples were collected prior to and at several time points post-intravenous injection. The detection of HAMA was performed with an in-house OV-TL 3 F(ab')2-based sandwich-type immunoradiometric assay (IRMA). The homologous IRMA demonstrated that 8 of 20 (40%) patients had developed HAMA responses after injection of Fab' fragments and that 14 of 73 (19%) patients had developed HAMA responses after F(ab')2 administration. The subclass of the measured HAMA was analysed in a limited number of samples, showing IgG or IgM as well as mixed responses. The kinetics of the HAMA responses varied greatly. Our study showed the relevance of the sampling time and frequency: HAMA responses can be easily underestimated with a low sampling frequency. The homologous IRMA described in this study was able to quantify the OV-TL 3-specific HAMA responses. With additional assays, the subclass of the HAMA could be further analysed. Remarkably, the fraction of HAMA responders after injection of OV-TL 3 Fab' fragments was in the same range as the proportion of HAMA responders after F(ab')2 administration.

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

PubMed

Abma, E; Peremans, K; De Vos, F; Bosmans, T; Kitshoff, A M; Daminet, S; Ni, Y; Dockx, R; de Rooster, H

2018-01-04

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients. © 2018 John Wiley & Sons Ltd.

Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium.

PubMed

Le Traon, G; Burgaud, S; Horspool, L J I

2008-04-01

Oral L-thyroxine (L-T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of L-T4 following administration of a solution (Leventa) was investigated in healthy dogs. L-T4 was absorbed fairly rapidly (t(max) 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 microg L-T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of L-T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with L-T4 oral administration delayed L-T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of L-T4 following administration of a tablet formulation was about 50% of that of the L-T4 solution. The pharmacokinetic properties of liquid L-T4 after oral administration support the use of a dose rate of 20 microg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.

Comparison of different administration of ketamine and intravenous tramadol hydrochloride for postoperative pain relief and sedation after pediatric tonsillectomy.

PubMed

Yenigun, Alper; Et, Tayfun; Aytac, Sirin; Olcay, Betul

2015-01-01

Tonsillectomy is the oldest and most frequently performed surgical procedure practiced by ear, nose, and throat physicians. In this study, our aim was to compare the analgesic effects of peritonsillar, rectal, as well as intravenous infiltration of ketamine and intravenous tramadol hydrochloride infiltration for postoperative pain relief and sedation after tonsillectomy in children. This randomized controlled study evaluated the effects of peritonsillar, intravenous, and rectal infiltration of ketamine in children undergoing adenotonsillectomy. One hundred twenty children who were categorized under American Society of Anesthesiologists classes I to II were randomized to 4 groups of 30 members each. Group 1 received intravenous (IV) ketamine (0.5 mg/kg), group 2 received rectal ketamine (0.5 mg/kg), group 3 received local peritonsillar ketamine (2 mg/kg), and the control group received IV tramadol hydrochloride infiltration (2 mg/kg). Children's Hospital of Eastern Ontario Pain Scale scores and Wilson sedation scale were recorded at minutes 1, 15, 30, 60 as well as hours 2, 12, and 24 postoperatively. The patients were interviewed on the day after the surgery to assess the postoperative pain and sedation. All the routes of infiltration of ketamine were as effective as those of tramadol hydrochloride (P > 0.05). A statistically significant difference was observed between IV infiltrations and all groups during the assessments at hours 6 and 24. The analgesic efficacy of IV ketamine was found especially higher at hours 6 and 24 (P(6) = 0.045, P(24) = 0.011). Perioperative, low-dose IV, rectal, or peritonsillar ketamine infiltration provides efficient pain relief without any adverse effects in children who would undergo adenotonsillectomy.

[Use of intravenous iron infusion in a gastroenterology day hospital: Indications, dosage and adverse effects].

PubMed

Dosal, Angelina; Calvet, Xavier; Moreno, Laura; López, María; Figuerola, Ariadna; Ruíz, Miquel Angel; Suárez, David; Gené, Emili; Miquel, Mireia; Villoria, Albert

2010-01-01

There are no data in the literature on the use of intravenous iron infusion in gastroenterology day hospitals. To determine the indications, dosage and tolerance of intravenous iron infusion in outpatients attending a gastroenterology day hospital. We retrospectively reviewed the medical records of patients who received intravenous iron infusion between August 2007 and July 2008. The indications, dosage, transfusion requirements, adverse effects and patients' clinical and laboratory data were recorded. During the study period, 111 patients (41% women, with a mean age of 63.8 ± 18 years) received intravenous iron infusions. The main causes of anemia indicating iron administration were portal hypertensive gastropathy (n=55), inflammatory bowel disease (n=22) and intestinal angiodysplasia (n=12). The patients received a total of 557 iron infusions with a mean dose of 1033 mg iron per patient. There were no adverse effects. Despite the treatment, 46 patients required transfusion. Iron and transfusion requirements and mortality were significantly higher in patients with liver cirrhosis than in the remainder of the study group. Intravenous iron therapy is frequently used in the gastroenterology day hospital. Most infusions were administered in patients with chronic iron loss. Patients with liver cirrhosis had the most severe anemia and underlying disease and the highest mortality.

Association of an Opioid Standard of Practice Intervention With Intravenous Opioid Exposure in Hospitalized Patients.

PubMed

Ackerman, Adam L; O'Connor, Patrick G; Doyle, Deirdre L; Marranca, Sheyla M; Haight, Carolyn L; Day, Christine E; Fogerty, Robert L

2018-06-01

Opioids are commonly used to treat pain in hospitalized patients; however, intravenous administration carries an increased risk of adverse effects compared with oral administration. The subcutaneous route is an effective method of opioid delivery with favorable pharmacokinetics. To assess an intervention to reduce intravenous opioid use, total parenteral opioid exposure, and the rate of patients administered parenteral opioids. A pilot study was conducted in an adult general medical unit in an urban academic medical center. Attending physicians, nurse practitioners, and physician assistants who prescribed drugs were the participants. Use of opioids was compared between a 6-month control period and 3 months following education for the prescribers on opioid routes of administration. Adoption of a local opioid standard of practice, preferring the oral and subcutaneous routes over intravenous administration, and education for prescribers and nursing staff on awareness of the subcutaneous route was implemented. The primary outcome was a reduction in intravenous doses administered per patient-day. Secondary measures included total parenteral and overall opioid doses per patient-day, parenteral and overall opioid exposure per patient-day, and daily rate of patients receiving parenteral opioids. Pain scores were measured on a standard 0- to 10-point Likert scale over the first 5 days of hospitalization. The control period included 4500 patient-days, and the intervention period included 2459 patient-days. Of 127 patients in the intervention group, 59 (46.5%) were men; mean (SD) age was 57.6 (18.5) years. Intravenous opioid doses were reduced by 84% (0.06 vs 0.39 doses per patient-day, P < .001), and doses of all parenteral opioids were reduced by 55% (0.18 vs 0.39 doses per patient-day, P < .001). In addition, mean (SD) daily parenteral opioid exposure decreased by 49% (2.88 [0.72] vs 5.67 [1.14] morphine-milligram equivalents [MMEs] per patient-day). The daily rate

Intravenous Narcotic Antagonists in Ambulatory Oral Surgery

PubMed Central

Greenfield, William; Granada, Margarito G.

1975-01-01

Results of a study indicate that significant respiratory depression can be produced by the intravenous administration of narcotics in the anesthetic management of oral surgery patients. Naloxone hydrochloride reversed this reaction in all instances. Naloxone is a unique narcotic antagonist in that it does not possess agonistic properties of its own, it is effective in reversing respiratory depression resulting from all commonly used narcotics and narcotic antagonists, it causes no undesirable side effects, and it acts as a placebo when administered to a patient who has not had a narcotic. The use of naloxone should be considered when a potent narcotic is administered to an ambulatory patient. PMID:19598479

Effects of intravenous gadolinium administration and flip angle on the assessment of liver fat signal fraction with opposed-phase and in-phase imaging.

PubMed

Yokoo, Takeshi; Collins, Julie M; Hanna, Robert F; Bydder, Mark; Middleton, Michael S; Sirlin, Claude B

2008-07-01

To assess the effects of intravenous gadolinium (Gd) and flip angle (FA) on liver fat quantification by opposed-phase (OP) and in-phase (IP) imaging. Our Institutional Review Board (IRB) approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant, retrospective, clinical study. We identified 79 patients in whom abdominal OP and IP gradient-echoes were obtained at 1.5T before and after Gd administration. All 79 patients were imaged at high FA (> or =70 degrees ); 57 were also imaged at low FA (< or =20 degrees ). Fat signal fraction (FSF) was calculated from pre- and post-Gd liver images for each subject and FA using the formula, FSF = (S(IP) - S(OP))/2S(IP), where S(IP) and S(OP) are the OP and IP signal intensities, respectively. The dataset pairs (pre-Gd vs. post-Gd; high-FA vs. low-FA) were compared using linear regression analysis. Before Gd, FSF was significantly greater at high FA than at low FA, with regression parameters (slope/intercept) of 1.27*/0.02*, where * indicates P value <0.01. After Gd, FSF was similar at high and low FA (0.99/-0.00). Gd administration caused an FA-dependent reduction in FSF, larger at high FA (0.68*/-0.03*) than at low FA (0.94, -0.01*). FSF by OP-IP imaging is highly dependent on FA before Gd, but this dependency is eliminated after administration of Gd. Gd appears to minimize the effect of T1-weighting and may improve the accuracy of liver fat quantification. (c) 2008 Wiley-Liss, Inc.

Efficacy of a single 40-mg intravenous dose of parecoxib for postoperative pain control after elective cesarean delivery: A double-blind randomized placebo-controlled trial.

PubMed

Inthigood, Nittaya; Lertbunnaphong, Tripop; Jaishuen, Atthapon

2017-01-01

The aim of this study was to determine the efficacy of a single 40-mg intravenous (i.v.) dose of parecoxib as an adjunctive analgesia to intrathecal morphine after elective cesarean delivery (CD). A total of 82 low-risk term pregnant women who were scheduled for elective CD during the June 2014-June 2015 study period were enrolled. Two hours after surgery, subjects were randomly assigned to receive either i.v. injection of 2 mL (40 mg) parecoxib (study group; n = 41) or 2 mL normal saline solution (control group; n = 41). Patient randomization into groups was determined by the hospital's central computer system. Outcome measurements included total postoperative supplemental meperidine consumption, recorded pain score by numeric pain rating scale at 6, 12, 18, and 24 h, postoperatively, and patient satisfaction. Patient characteristics and pregnancy outcomes were comparable between groups. Total postoperative meperidine consumption was not significantly different between groups (12.7 ± 18.8 mg vs 8.3 ± 16.7 mg; P > 0.05). Compared with control, the study group was significantly less likely to experience moderate to severe postoperative pain (score ≥ 4) at 6 h (0% vs 21.9%; P = 0.002). Study group patients reported higher satisfaction than control group patients (median score: 8 vs 6; P < 0.01). No patients in either group reported adverse effects from their assigned intervention. Parecoxib did not demonstrate effectiveness in reducing patient requirement for supplementary meperidine after CD. However, administration of a single 40-mg dose of i.v. parecoxib after elective CD demonstrated effectiveness in reducing pain scores, with a resulting increase in patient satisfaction. © 2016 Japan Society of Obstetrics and Gynecology.

Pharmacokinetics and distribution of ceftazidime to milk after intravenous and intramuscular administration to lactating female dromedary camels (Camelus dromedarius).

PubMed

Goudah, Ayman M; Hasabelnaby, Sherifa M

2013-08-01

To determine the plasma disposition kinetics, absolute bioavailability, and milk concentrations of ceftazidime in healthy lactating female dromedary camels (Camelus dromedarius) following IV and IM administration of a single dose of 10 mg/kg (4.5 mg/lb). Prospective crossover study. 8 healthy adult lactating female dromedary camels. Camels received ceftazidime (10 mg/kg) IV and IM in a crossover study design with a 15-day washout period between treatments. Plasma and milk samples were collected at predetermined times for 48 hours after drug administration and analyzed by use of high-performance liquid chromatography. A 2-compartment open model best represented the plasma concentration-versus-time data after IV and IM administration of ceftazidime to camels. Plasma ceftazidime concentrations decreased biexponentially after IV administration with mean distribution and elimination half-lives of 0.3 hours and 2.85 hours, respectively. After IM administration, the mean maximum plasma concentration of ceftazidime was 32.43 μg/mL (1.21 hours after administration), mean elimination half-life was 3.20 hours, mean residence time was 4.84 hours, and mean systemic bioavailability was 93.72%. Distribution of ceftazidime from plasma to milk was rapid and extensive as indicated by the ratio of the area under the milk concentration-versus-time curve to the area under the plasma concentration-versus-time curve and the ratio of the maximum milk concentration to the maximum plasma concentration of ceftazidime after IV and IM administration. Results suggested that ceftazidime may be a useful treatment for female camels with mastitis caused by susceptible microorganisms.

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PubMed

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats.

PubMed

Rodrigo-Mocholí, D; Escudero, E; Belda, E; Laredo, F G; Hernandis, V; Marín, P

2018-07-01

To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats. Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded. The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery. Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration

Simultaneous oral therapeutic and intravenous 14C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin

PubMed Central

Boulton, David W.; Kasichayanula, Sreeneeranj; Keung, Chi Fung (Anther); Arnold, Mark E.; Christopher, Lisa J.; Xu, Xiaohui (Sophia); LaCreta, Frank

2013-01-01

Aim To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C‐microdose/therapeutic oral dosing (i.v.micro + oraltherap). Methods The Fp.o. values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography‐tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively. Results The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap. Conclusions Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability. PMID:22823746

Modelling Framework and Assistive Device for Peripheral Intravenous Injections

NASA Astrophysics Data System (ADS)

Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar

2016-02-01

Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

Repackaging of Intravenous Fat Emulsions: A Clinical Conundrum.

PubMed

Cober, M Petrea

2016-10-01

To accommodate small fluid volumes, repackaging of intravenous fat emulsions (IVFEs) is frequently performed in institutions providing parenteral nutrition to neonates and smaller pediatric patients. However, some consider this an unsafe practice. Concerns for potential administration errors leading to an overdose of IVFEs are weighed against the potential for microbial contamination from the repackaging process. The clinician providing pediatric nutrition support should tailor repackaging practices to ensure patient safety and quality. This discussion aims to describe the strengths and limitations surrounding IVFE repackaging to provide guidance regarding the practice. © 2016 American Society for Parenteral and Enteral Nutrition.

Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

PubMed

Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

2018-05-01

The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

First report on the pharmacokinetic profile of nimbolide, a novel anticancer agent in oral and intravenous administrated rats by LC/MS method.

PubMed

Baira, Shandilya Mahamuni; Khurana, Amit; Somagoni, Jaganmohan; Srinivas, R; Godugu, Chandraiah; Talluri, M V N Kumar

2018-06-02

Nimbolide is a novel, natural compound with promising potential as a drug candidate for anticancer activity. It is isolated from the Indian traditional medicinal plant Azadirachta indica popularly known as neem. The present study was undertaken to explore the oral bioavailability and pharmacokinetic characteristics of nimbolide in rats using the LC/QTOF/MS method. A simple protein precipitation method using acetonitrile was employed for extracting nimbolide from rat plasma. The chromatographic separation of nimbolide and the internal standard (regorafenib) was attained on an Aquity BEH C18 column (100 × 2.1 mm, 2.7 μm), using ACN and 0.1% of formic acid in water as mobile phase components in a gradient elution mode at a flow rate of 0.45 mL/min over a short run time of 4 min. A mass detection was carried out using target ions of [M + H] + at m/z 467.2074 for nimbolide and m/z 483.0847 for the internal standard. The LC/MS method was validated and all the parameters were found well within the specified limits. The calibration curve was constructed in the range of 1-1000 ng/mL. The method shows good accuracy (91.66-97.12%) and precision (intra 2.21-6.92% CV and inter-day 2.56-4.62% CV). This developed LC/MS method was effectively applied to the pharmacokinetic study of nimbolide upon oral and intravenous administration in rats. In concordance with its physicochemical properties and high lipophilicity, we found that it shows poor oral absorption at different doses (10, 30 and 50 mg/kg). As expected, higher plasma levels were observed upon intravenous (10 mg/kg) administration. This method can be extended for evaluation of drug interaction and drug metabolism in rats as well as in humans. Moreover, our rapid and sensitive method may cater the need to accelerate the preclinical formulation development and lead optimization for future drug development of this potent anticancer agent. Further, our oral bioavailability studies demonstrated that

Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.

PubMed

Zufferey, Paul J; Lanoiselée, Julien; Chapelle, Céline; Borisov, Dmitry B; Bien, Jean-Yves; Lambert, Pierre; Philippot, Rémi; Molliex, Serge; Delavenne, Xavier

2017-09-01

Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss. This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy. The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, -77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid. A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss.

The use of temazepam elixir in surgical dental sedation: a comparison with intravenous midazolam.

PubMed

Skelly, A M; Girdler, N M; File, S E

1992-02-22

Out-patients attending for removal of at least one lower third molar were randomly allocated to treatment with temazepam elixir (n = 7) or intravenous midazolam (n = 8), as well as local analgesia. Patients were tested prior to drug administration and at the end of surgery. Both drugs increased heart rate and midazolam also decreased diastolic blood pressure. The two drugs caused significant, equal increases in ratings of sedation, but the reduction of anxiety was significant only for midazolam. There was significant amnesia for material presented after drug administration, as well as for dental events and this was significantly greater for midazolam. The effects of these drugs in dental patients were compared with those in normal volunteers treated in an identical manner, but without oral surgery. The drugs had similar significant cardiovascular and amnesic effects in the volunteers and the same effects on mood ratings, even though volunteers and patients differed in their pretreatment levels of anxiety and discontent. The dentist's ratings of the sedation and operating conditions were excellent in both cases. Thus temazepam elixir provided a useful sedative for oral surgery, avoiding the complications of intravenous administration. However, for equivalent levels of sedation, midazolam had greater anxiolytic and amnesic effects than temazepam.

Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration.

PubMed

Suga, Yasuyo; Takehana, Kenji

2017-09-01

S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; β-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b + TIM-4 + cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b + TIM-4 + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

76 FR 67192 - Administration on Children, Youth and Families Announces the Award of a Single-Source Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Administration on Children, Youth and Families Announces the Award of a Single-Source Program Expansion Supplement Grant to..., comprehensive outreach and increased capacity through technology improvements. STATUTORY AUTHORITY: Part C...

Enteral vs. intravenous ICU sedation management: study protocol for a randomized controlled trial.

PubMed

Mistraletti, Giovanni; Mantovani, Elena S; Cadringher, Paolo; Cerri, Barbara; Corbella, Davide; Umbrello, Michele; Anania, Stefania; Andrighi, Elisa; Barello, Serena; Di Carlo, Alessandra; Martinetti, Federica; Formenti, Paolo; Spanu, Paolo; Iapichino, Gaetano

2013-04-03

A relevant innovation about sedation of long-term Intensive Care Unit (ICU) patients is the 'conscious target': patients should be awake even during the critical phases of illness. Enteral sedative administration is nowadays unusual, even though the gastrointestinal tract works soon after ICU admission. The enteral approach cannot produce deep sedation; however, it is as adequate as the intravenous one, if the target is to keep patients awake and adapted to the environment, and has fewer side effects and lower costs. A randomized, controlled, multicenter, single-blind trial comparing enteral and intravenous sedative treatments has been done in 12 Italian ICUs. The main objective was to achieve and maintain the desired sedation level: observed RASS = target RASS ± 1. Three hundred high-risk patients were planned to be randomly assigned to receive either intravenous propofol/midazolam or enteral melatonin/hydroxyzine/lorazepam. Group assignment occurred through online minimization process, in order to balance variables potentially influencing the outcomes (age, sex, SAPS II, type of admission, kidney failure, chronic obstructive pulmonary disease, sepsis) between groups. Once per shift, the staff recorded neurological monitoring using validated tools. Three flowcharts for pain, sedation, and delirium have been proposed; they have been designed to treat potentially correctable factors first, and, only once excluded, to administer neuroactive drugs. The study lasted from January 24 to December 31, 2012. A total of 348 patients have been randomized, through a centralized website, using a specific software expressly designed for this study. The created network of ICUs included a mix of both university and non-university hospitals, with different experience in managing enteral sedation. A dedicated free-access website was also created, in both Italian and English, for continuous education of ICU staff through CME courses. This 'educational research' project aims both to

Successful treatment of ciguatera fish poisoning with intravenous mannitol.

PubMed

Palafox, N A; Jain, L G; Pinano, A Z; Gulick, T M; Williams, R K; Schatz, I J

1988-05-13

Twenty-four patients with acute ciguatera fish poisoning were treated with intravenous mannitol, and each patient's condition improved dramatically. All exhibited marked lessening of neurologic and muscular dysfunction within minutes of the administration of mannitol. Gastrointestinal symptoms disappeared more slowly. Two patients in coma and one in shock responded within minutes, with full recovery after infusion. Although these observations were empiric and uncontrolled and the mechanism of action of mannitol in this disease is unclear, mannitol should be considered for initial use in patients with significant illness and morbidity from ciguatera fish poisoning.