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Sample records for single dose albendazole

  1. Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

    PubMed Central

    Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

    2011-01-01

    Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

  2. Tolerability and efficacy of single dose albendazole, diethylcarbamazine citrate (DEC) or co-administration of albendazole with DEC in the clearance of Wuchereria bancrofti in asymptomatic microfilaraemic volunteers in Pondicherry, South India: a hospital-based study

    PubMed Central

    Pani, SP; Subramanyam Reddy, G; Das, LK; Vanamail, P; Hoti, SL; Ramesh, J; Das, PK

    2002-01-01

    Background The tolerability and efficacy of single dose albendazole (400 mg), diethylcarbamazine citrate (DEC) (6 mg/kg bodyweight) or co-administration of albendazole (400 mg) + DEC (6 mg/kg bodyweight) was studied in 54 asymptomatic Wuchereria bancrofti microfilaraemic volunteers in a double blind hospital-based clinical study. Results There was no significant difference in the overall incidence of adverse reactions between the three drug groups [42.1% (albendazole), 52.9% (DEC) and 61.1% (albendazole + DEC); P > 0.05]. The mean score of adverse reaction intensity did not differ significantly between the DEC and albendazole + DEC groups. However, the values in these two groups were significantly higher compared to that of albendazole alone [1.8 ± 3.0 (albendazole) vs. 5.6 ± 7.1 (DEC), 6.7 ± 6.6 (albendazole + DEC); P < 0.05]. By day 360 post-therapy there was no significant difference between the three drug groups in relation to the clearance of microfilaria [26.3% (albendazole), 17.6% (DEC), 27.8% (albendazole + DEC)], reduction in geometric mean parasite density [94.7% (albendazole), 89.5% (DEC), 95.4% (albendazole + DEC)] or reduction in filarial antigenaemia [83% (albendazole), 87% (DEC), 75% (albendazole + DEC)]. Furthermore, there was a significant decrease in mean geometric parasite density (P < 0.05) as well as antigenaemia optical density values (P < 0.01) between pre-therapy levels and day 360 post-therapy in all three groups. Conclusions This study has shown that single dose albendazole (400 mg) has similar efficacy in the clearance of microfilaria as that of DEC or the co-administration of the two drugs. The results strengthen the rationale of using albendazole for mass annual single dose administration for the control of transmission of lymphatic filariasis. PMID:12537598

  3. Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole

    PubMed Central

    Abdel-tawab, Ahmed M; Bradley, Mark; Ghazaly, Essam A; Horton, John; El-Setouhy, Maged

    2009-01-01

    AIMS Albendazole (ABZ) is used in several anthelminthic drug programmws. ABZ side-effects are generally mild, but ABZ-induced pancytopenia may be serious. In filariasis programmes, it may be necessary to administer ABZ to breastfeeding women. Few data are available on safety of ABZ for breastfed infants. In addition, the pharmacokinetics of ABZ and its metabolites in human milk is insufficiently investigated. The aim was to study pharmacokinetics of ABZ and its metabolites [ABZ sulphoxide (ABSX) and ABZ sulphone] in the breast milk lactating women after one single oral dose of ABZ. METHODS Thirty-three lactating women (age 18–40 years) participated in the study. They received a single oral 400-mg dose of ABZ. Five milk samples were taken at 0, 6, 12, 24 and 36 h. One serum sample was taken after 6 h. Samples were analysed using high-performance liquid chromatography and pharmacokinetic analysis was performed. RESULTS ABZ was detectable in milk samples 6 h after the oral dose. The mean concentration of serum ABZ was 63.7 ± 11.9 ng ml−1. The pharmacokinetic parameters for ABSX were calculated as follows: 351.9 ± 32.4 ng ml−1, 6.9 ± 0.5 h, 12.4 ± 2.2 h and 5190.3 ± 482.8 ng*h ml−1 for Cmax, Tmax, t½ and AUC0–36, respectively. The milk-to-serum ratios (range) for ABZ and ABSX were 0.9 (0.2–6.5) and 0.6 (0.1–1.5), respectively. CONCLUSIONS After an oral dose of 400 mg, ABZ and ABSX attain low concentrations in breast milk that are unlikely to be considered harmful for the breastfed infant. PMID:19916998

  4. Low Efficacy of Single-Dose Albendazole and Mebendazole against Hookworm and Effect on Concomitant Helminth Infection in Lao PDR

    PubMed Central

    Soukhathammavong, Phonepasong Ayé; Sayasone, Somphou; Phongluxa, Khampheng; Xayaseng, Vilavanh; Utzinger, Jürg; Vounatsou, Penelope; Hatz, Christoph; Akkhavong, Kongsap; Keiser, Jennifer; Odermatt, Peter

    2012-01-01

    Background Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. Methodology We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21–23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. Principal Findings Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2–0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively). Conclusions/Significance Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. Clinical Trial Registration Current Controlled Trials ISRCTN29126001 PMID:22235353

  5. Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide

    PubMed Central

    2013-01-01

    Background Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. Methods We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Results Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Conclusions Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects. PMID:23289920

  6. A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.

    PubMed Central

    Belizario, V. Y.; Amarillo, M. E.; de Leon, W. U.; de los Reyes, A. E.; Bugayong, M. G.; Macatangay, B. J. C.

    2003-01-01

    OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems. PMID:12640474

  7. Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

    PubMed Central

    Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

    2011-01-01

    Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

  8. Albendazole in the treatment of intestinal helminthiasis in children.

    PubMed

    Misra, P K; Pande, N K; Jagota, S C

    1985-01-01

    A single dose of 2% albendazole suspension (400 mg in 20 ml) was administered to 77 patients (42 males and 35 females), ages ranging between 2 to 12 years, with helminthic infections. Ascariasis was the most prevalent infection. Patients were followed-up for 3 weeks. The results showed that albendazole was highly effective against Ascaris lumbricoides, Ancylostoma duodenale and Enterobius vermicularis. Significant improvement was also observed in patients having infections due to Trichuris trichiura. Albendazole was well tolerated and did not produce any significant side-effects. Single dose albendazole appears to be appropriate for mass chemotherapy to control intestinal nematode infections in highly infected communities. PMID:4028809

  9. Efficacy of albendazole against giardiasis in dogs.

    PubMed

    Barr, S C; Bowman, D D; Heller, R L; Erb, H N

    1993-06-01

    Efficacy of albendazole for treating giardiasis in dogs was assessed in 3 experiments. In experiment 1, Giardia cysts were cleared from feces of 5 of 7 dogs (as determined by the zinc-sulfate concentration technique) after the dogs received a single dose of albendazole (25 mg/kg of body weight, PO), whereas feces of 3 of 7 dogs became clear of cysts without treatment. In experiment 2, feces of 5 of 5 dogs became clear of cysts after albendazole treatment (25 mg/kg, PO, q 12 h for 4 doses); feces of 1 of 5 untreated control dogs became clear. In experiment 3, feces of 18 of 20 dogs became clear of cysts after albendazole (25 mg/kg, PO, q 12 h for 4 doses) was given; none of the 20 control dogs had feces clear of cysts. Signs of toxicosis were not observed in any dog. These results indicate that a single dose of albendazole (25 mg/kg, PO) is not effective for treating giardiasis in dogs. However, 4 doses of albendazole (25 mg/kg, PO, q 12 h) are highly effective and non-toxic for treatment of giardiasis in dogs. PMID:8323064

  10. Clinical pharmacokinetics of albendazole in children with neurocysticercosis.

    PubMed

    Jung, H; Sánchez, M; González-Astiazarán, A; Martínez, J M; Suástegui, R; González-Esquivel, D F

    1997-01-01

    The pharmacokinetics of albendazole sulphoxide, the main metabolite of albendazole, were studied in eight children with brain cysticercosis. Albendazole was given as a single oral dose of 15 mg per kg body weight (Zentel suspension; Smith Kline & Beecham, Philadelphia, PA). Blood samples were taken during 24 h and analyzed by high performance liquid chromatography. Plasma levels showed great interindividual variation. Maximum plasma levels for albendazole sulphoxide ranged from 0.2-1.0 microg/mL. A double peak was found in four children. The half-life for albendazole sulphoxide was from 2.3-8.3 hours and mean residence time values were from 5. 1-13.6 hours. These values are shorter than those found in adults. The results suggest that when treating children with neurocysticercosis, albendazole should be administered three times a day rather than twice daily as is currently done in Mexico. PMID:10423586

  11. A Randomized Controlled Trial of Increased Dose and Frequency of Albendazole with Standard Dose DEC for Treatment of Wuchereria bancrofti Microfilaremics in Odisha, India

    PubMed Central

    Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-01-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  12. A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

    PubMed

    Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-03-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  13. Pharmacokinetics of albendazole in sheep.

    PubMed

    Marriner, S E; Bogan, J A

    1980-07-01

    The concentrations of albendazole and its two major metabolites, the sulfoxide and sulfone, were measured in plasma and in ruminal and abomasal fluid of three sheep (surgically prepared with permanent ruminal and abomasal cannulae) orally given albendazole as a suspension at a dose rate of 10 mg/kg. Albendazole was not detectable in plasma at any time in one sheep (detection limit, 0.02 micrograms/ml) and in the other sheep, only transiently detectable. Albendazole sulfoxide was detectable in plasma and in abomasal fluid at mean peak concentrations of 3.2 and 26.2 micrograms/ml, respectively, 20 hours after administration. It is probable that much of the anthelmintic activity of albendazole in sheep is due to the metabolically formed sulfoxide and sulfone. PMID:7436109

  14. Efficacy of pharmacokinetic interactions between piperonyl butoxide and albendazole against gastrointestinal nematodiasis in goats.

    PubMed

    Kumbhakar, N K; Sanyal, P K; Rawte, D; Kumar, D; Kerketta, A E; Pal, S

    2016-09-01

    To test the hypothesis that modulation of hepatic microsomal sulphoxidation and sulphonation by the cytochrome P450 inhibitor piperonyl butoxide could increase bioavailability of albendazole, the present study was undertaken to understand the pharmacokinetics of albendazole in goats at a dose of 7.5 mg kg- 1 body weight with and without co-administration with piperonyl butoxide at 63.0 mg kg- 1 body weight. Plasma albendazole sulphoxide metabolite, the anthelmintically active moiety, reached its maximum concentration of 0.322 ± 0.045 μg ml- 1 and 0.384 ± 0.013 μg ml- 1 at 18 h and 24 h after administration of albendazole alone and co-administration of albendazole with piperonyl butoxide, respectively. Analysis of the data revealed statistically increased albendazole sulphoxide levels at 24 (P 0.05) in values of maximum concentration (normal and calculated) could be observed between groups of goats. However, values of time to reach the concentration maximum (normal and calculated), area under the concentration-time curve (0-∞ and calculated), minimum residence time, distribution half-life, elimination half-life and total area under the first movement of plasma drug concentration-time curve were significantly higher (P <  0.05) in plasma levels of albendazole sulphoxide in goats following single oral co-administration of albendazole with piperonyl butoxide. The faecal egg count reduction and lower 95% confidence limit for the group treated with albendazole alone were 97 and 68%, while for co-administration of albendazole and piperonyl butoxide the values were 99 and 97%, respectively. The ED50 for egg hatch was 0.196, indicating suspected resistance to benzimidazole anthelmintics. The drug combination proved efficacious against an albendazole-resistant nematode parasite population in goats. PMID:26566193

  15. Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

    PubMed Central

    Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.

    2016-01-01

    Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331

  16. The antimicrosporidial activity of albendazole.

    PubMed

    Haque, A; Hollister, W S; Willcox, A; Canning, E U

    1993-09-01

    The antimicrosporidial activity of albendazole was tested on Nosema bombycis in vitro in Spodoptera frugiperda cells and in vivo in Heliocoverpa zea larvae and pupae. Significant reductions in the percentage of infected S. frugiperda cells were obtained using a concentration of 5.3 micrograms/ml albendazole in tissue culture medium but recrudescence occurred after the drug was withdrawn from the cultures. Significant reductions in the number of spores harvested from 6th-instar larvae or pupae were obtained when doses of 0.2 to 4.0 mg were incorporated into the diet but, with the lower doses, some resurgence of infection occurred in pupae after cessation of drug intake. Established infections were almost eliminated from 6th-instar larvae and pupae after consumption of 2 or 4 mg albendazole and infections were not established at all when 4 mg was consumed concurrently with the infective spores. Even at the highest dose albendazole had no deleterious effect on the growth and viability of H. zea. Clumped chromatin in the nuclei of meronts, revealed by electron microscopy, reflected the selective anti-tubulin activity of albendazole and there was massive disorganization of sporogonic development. PMID:8228321

  17. Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy.

    PubMed

    Moreno, L; Echevarria, F; Muñoz, F; Alvarez, L; Sanchez Bruni, S; Lanusse, C

    2004-01-01

    The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n = 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO(2)) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO(2) were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (< 24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A

  18. [Treatment of hydatidosis with albendazol].

    PubMed

    Magnussen, P; Gelletlie, R; Bygbjerg, I C

    1989-10-23

    Eight patients with hydatidosis treated with albendazol in daily doses of 10 mg/kg daily in courses of 28 days (4-6 courses) were analysed. The patients came from Morocco, Spain, Turkey and Yugoslavia. Seven patients had a cyst (or cysts) in the liver and one had also cysts in the kidneys. One patient had cysts in the muscles of the extremities. As assessed by ultrasonic scanning, computed tomography of the cysts, general condition, serology and the presence of hydatid antigen in the serum, treatment was effective in six patients. One patient developed an allergic reaction to albendazol. All of the patients had varying degrees of liver involvement which were reversible. Neutropenia did not occur. Various parameters for assessing the therapeutic effect are mentioned. Albendazol appears to be effective in the treatment of non-operable hydatid disease and to prevent recurrence after surgery. PMID:2588356

  19. [The experimental chemotherapy of larval alveolar echinococcosis. The search for an optimal regimen of albendazole use].

    PubMed

    Dzhabarova, V I; Novik, T S

    1999-01-01

    The antiechinococcal activity of albendazole resynthesized at the E. I. Martsinovskiĭ Institute of Medical Parasitology and Tropical Medicine was studied on infection models in rats and mouse in different experimental modifications. The efficiency of the therapy was determined in relation to the dose of the drug and its routes administrations, to the single or intermittent daily dose, to the presence or absence of intervals in the treatment regimen, to dosage forms. The trials indicated that albendazole was most active against larval alveolar echinococcosis of mice or cotton rats when it was used with their feed, i.e. through the gastrointestinal tract. PMID:10414050

  20. ESR identification of gamma-irradiated albendazole

    NASA Astrophysics Data System (ADS)

    Çolak, Seyda

    2010-01-01

    The use of ionizing radiation for sterilization of pharmaceuticals is a well-established technology. In the present work, the spectroscopic and kinetic features of the radicals induced in gamma-irradiated solid albendazole samples is investigated at different temperatures in the dose range of 3-34 kGy by electron spin resonance (ESR) spectroscopy. Irradiation with gamma radiation produced two different radical species in albendazole. They were fairly stable at room temperature but relatively unstable above room temperature, giving rise to an unresolved ESR spectrum consisting of three resonance peaks centered at g=2.0057. Decay activation energies of the contributing radical species were calculated to be 47.8 (±13.5) and 50.5 (±9.7) kJ/mol using the signal intensity decay data derived from annealing studies performed at high temperatures. A linear function of the applied dose was found to best describe the experimental dose-response data. Albendazole does not present the characteristics of good dosimetric materials. However, the discrimination of irradiated albendazole from its unirradiated form was possible even 6 months after storage in normal conditions. Based on these findings, it is concluded that albendazole and albendazole-containing drugs can be safely sterilized by gamma radiation and that ESR spectroscopy could be successfully used as a potential technique for monitoring their radiosterilization.

  1. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs. PMID:26756920

  2. Determination of albendazole and metabolites in silkworm Bombyx mori hemolymph by ultrafast liquid chromatography tandem triple quadrupole mass spectrometry.

    PubMed

    Li, Li; Xing, Dong-Xu; Li, Qing-Rong; Xiao, Yang; Ye, Ming-Qiang; Yang, Qiong

    2014-01-01

    Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905-0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%-103.83% for ABZ, 66.51%-108.51% for ABZSO, 96.85%-105.6% for ABZSO2 and 96.46%-106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time. PMID:25255321

  3. A randomised multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children.

    PubMed

    Dutta, A K; Phadke, M A; Bagade, A C; Joshi, V; Gazder, A; Biswas, T K; Gill, H H; Jagota, S C

    1994-01-01

    A randomised control multicentre study to compare the safety and efficacy of albendazole and metronidazole in the treatment of giardiasis in children is reported. One hundred and fifty children of either sex (age range: 2-10 years) were randomised to receive either a single dose of 400 mg of albendazole suspension, or 22.5 mg/kg/day of metronidazole in 3 divided doses for 5 consecutive days. At the end of therapy, majority of children in both treatment groups were symptom free. Two days after completion of therapy, 97% of children in both treatment groups were giardia free in the stools. Side effects were noted in 3 children in the albendazole group, and in 20 children in the metronidazole group. We conclude that albendazole suspension is as effective as metronidazole in the treatment of giardial infection in children. It is safe and has fewer side effects as compared to metronidazole. PMID:7721374

  4. Albendazole therapy and reduced decline in haemoglobin concentration during pregnancy (Sierra Leone).

    PubMed

    Torlesse, H; Hodges, M

    2001-01-01

    WHO recommends that anthelmintic treatment be included in strategies to improve maternal nutrition in areas where hookworms are endemic and anaemia is prevalent. At present, few countries have adopted this recommendation, partly owing to the lack of data to support the adverse effects of hookworms on maternal health. A longitudinal study was conducted on 125 women in Sierra Leone (in 1995/96) to measure the impact of single-dose albendazole (400 mg) and daily iron-folate supplements (36 mg iron and 5 mg folate) on haemoglobin and serum ferritin concentration during pregnancy. Women who received both albendazole and iron-folate supplements experienced no significant change (P > 0.05) in the prevalence of anaemia and iron-deficiency anaemia between the first and third trimesters. These prevalence levels significantly increased (P < 0.05) in women who received either albendazole or iron-folate supplements or neither. After controlling for baseline haemoglobin concentration and season, the mean decline in haemoglobin concentration between the first and third trimester in women who received albendazole was 6.6 g/L less than in women who received the control (P = 0.0034). The corresponding value for iron-folate supplements was 13.7 g/L haemoglobin (P < 0.001). The effects of albendazole and iron-folate supplements were additive. These findings lend support to WHO's recommendation for anthelmintic treatment during pregnancy. PMID:11355560

  5. [Ascariasis: comparison of the therapeutic efficacy between paico and albendazole in children from Huaraz].

    PubMed

    López De Guimaraes, D; Neyra Llanos, R S; Romero Acevedo, J H

    2001-01-01

    A therapeutical clinical trial was designed to study the effectiveness of Paico and Albendazole, for the treatment of ascariasis in a group of 60 children, between 3 and 14 years old, from a rural community in Huaraz. It was carried out between May and August, 2000. The sample was randomly divided into 30 cases for Paico and 30 for Albendazole, the criteria for entering the trial being a positive examination for Ascaris lumbricoides in feces. The treatment consisted in Paico juice: 1 ml/Kg for less than 10 Kg, and 2 ml/Kg in larger children, one dose before breakfast, for three consecutive days. The Albendazole was administered in a single dose of 400 mg in those over five years of age, and 200 mg in younger children. The effectiveness was evaluated qualitatively (the disappearance of the ascaris eggs from the feces) and quantitatively (decrease in the parasitic burden); in the stool examinations carried out in all cases on entering the study and 15 days after the treatment. All the stool samples were processed in the Referential Laboratory of the Regional Health Authority in Ancash. The qualitative effectiveness between Paico and Albendazole for the eradication of ascariasis was similar at 86.7%. The quantitative effectiveness was 59.5% for Paico and 58.3% for Albendazole. However, it was observed that, unlike Albedazole, Paico is 100% effective in the treatment of Hymenolepsis nana. Adverse effects were presented in 23.3% of the cases for both drugs. It is concluded that, although Paico and Albendazole have a similar effectiveness against Ascaris lumbricoides, Paico has the additional benefit of being effective against Hymenolepsis nana. PMID:11818981

  6. Rapid Re-Infection with Soil-Transmitted Helminths after Triple-Dose Albendazole Treatment of School-Aged Children in Yunnan, People's Republic of China

    PubMed Central

    Yap, Peiling; Du, Zun-Wei; Wu, Fang-Wei; Jiang, Jin-Yong; Chen, Ran; Zhou, Xiao-Nong; Hattendorf, Jan; Utzinger, Jürg; Steinmann, Peter

    2013-01-01

    Post-treatment soil-transmitted helminth re-infection patterns were studied as part of a randomized controlled trial among school-aged children from an ethnic minority group in Yunnan province, People's Republic of China. Children with a soil-transmitted helminth infection (N = 194) were randomly assigned to triple-dose albendazole or placebo and their infection status monitored over a 6-month period using the Kato-Katz and Baermann techniques. Baseline prevalence of Trichuris trichiura, Ascaris lumbricoides, hookworm, and Strongyloides stercoralis were 94.5%, 93.3%, 61.3%, and 3.1%, respectively, with more than half of the participants harboring triple-species infections. For the intervention group (N = 99), the 1-month post-treatment cure rates were 96.7%, 91.5%, and 19.6% for hookworm, A. lumbricoides, and T. trichiura, respectively. Egg reduction rates were above 88% for all three species. Rapid re-infection with A. lumbricoides was observed: the prevalence 4 and 6 months post-treatment was 75.8% and 83.8%, respectively. Re-infection with hookworm and T. trichiura was considerably slower. PMID:23690551

  7. Albendazole in the treatment of intestinal helminthiasis in children.

    PubMed

    Prasad, R; Mathur, P P; Taneja, V K; Jagota, S C

    1985-01-01

    One hundred sixteen children between 2 and 15 years of age entered a clinical trial of albendazole after examination of their stools revealed ova of one or more intestinal helminths. The drug was administered as a single 400-mg dose (20 ml of 2% suspension) to all the patients except those having Hymenolepis nana infection, who received treatment for three consecutive days. The stools were reexamined on days 7 and 14 posttreatment and after three months for Taenia infections. Patients were considered cured if all parasitological examinations of the feces were negative after treatment. After a single oral dose, albendazole was highly effective in ascariasis (91.9%), ancylostomiasis caused by Ancylostoma duodenale (87.2%), and H nana infection (71.4%). The drug was well tolerated, and no abnormalities were observed in hematological or blood chemistry values. Since the drug is safe and effective as a single-dose treatment of common helminthic infections, it should be considered for mass therapy in the community. PMID:3986860

  8. Efficacy of closantel plus albendazole liquid suspension against natural infection of gastrointestinal parasites in camels.

    PubMed

    Al-Qudah, K M; Sharif, L A; Al-Rawashdeh, O F; Al-Ani, F K

    1999-03-31

    Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites. The camels involved were 15 pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal samples were collected per rectum from all camels at the time of treatment and again 14 and 42 days post treatment. Fecal egg counts and generic determination of third stage larvae was performed. Results indicated that six different species of gastrointestinal tract parasites were identified in camels. Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100%, 100%, 98% and 77% for Haemonchus longistipes, Ascaris spp., Monezia expansa and Fasciola hepatica, respectively. However, administration of the drug twice on the base of 2 weeks apart significantly raised the efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with various parasites. Camels were not adversely affected by treatment. PMID:10321589

  9. A study of the efficacy and safety of albendazole (Zentel) in the treatment of intestinal helmenthiasis in Kenyan children less than 2 years of age.

    PubMed

    Pamba, H O; Bwibo, N O; Chunge, C N; Estambale, B B

    1989-03-01

    One hundred children comprising of 57 males and 43 females aged between 8 and 24 months entered the study. 46 children had single and 54 children had multiple helminth infections. All children received albendazole 200 mg (10 ml) suspension as a single dose. Albendazole proved very effective and safe in the treatment of single and multiple helminth infections in children under 2 years of age, achieving cure rates of 100% in both Ascaris lumbricoides and Necator americanus respectively, 83% in Trichuris trichiura and 66% in Hymenolepis nana. Treatment of polyparasitism appears to be of benefit in improving nutritional status using haemoglobin concentrations as an index. PMID:2591328

  10. Efficacy of clorsulon and albendazole against Fascioloides magna in naturally infected white-tailed deer.

    PubMed

    Foreyt, W J; Drawe, D L

    1985-12-01

    The efficacy of clorsulon and of albendazole against Fascioloides magna were evaluated in 36 naturally infected white-tailed deer (Odocoileus virginianus) in southern Texas. A single oral dose of clorsulon suspension (12 to 30 mg/kg of body weight; mean = 24 mg/kg) was given to each deer and killed 153 (92%) of 167 mature flukes and 4 (80%) of 5 immature flukes recovered at necropsy. A single oral dose of albendazole paste (17 to 46 mg/kg; mean = 26 mg/kg) was given to each deer and killed 148 (89%) of 167 mature flukes and 4 (67%) of 6 immature flukes recovered at necropsy. In 82 nontreated control deer, 271 live flukes were recovered; dead flukes were not recovered. PMID:4077630

  11. Albendazole therapy for experimentally induced Paragonimus kellicotti infection in cats.

    PubMed

    Dubey, J P; Hoover, E A; Stromberg, P C; Toussant, M J

    1978-06-01

    The effect of albendazole therapy was studied in 6 cats with pulmonary paragonimiasis induced by experimental inoculation of metacercariae (25/cat) of Paragonimus kellicotti. At 76 to 101 days after they were inoculated, 5 cats were administered an oral aqueous suspension of albendazole in 2 divided doses totaling 20 mg (2 cats), 50 mg (1 cat), or 100 mg (2 cats)/kg of body weight each day for 14 to 21 days. The 6th cat (control) was not administered albendazole. Nine days after cats were given the 50- and 100-mg/kg dosages, Paragonimus ova were not seen in the feces of 3 cats. There was marked reduction in ova production in the feces of the 2 cats administered 20 mg/kg of albendazole. Live flukes were not recovered from the lungs of 3 cats necropsied 4 or 5 weeks after dosing with 50 or 100 mg/kg, but the lungs of the 2 cats administered 20 mg of albendazole/kg yielded 9 and 7 apparently viable flukes. Seventeen live flukes were recovered from the control cat not treated with albendazole. In 4 noninoculated normal cats administered 20 mg (1 cat), 100 mg (1 cat), and 200 mg (2 cats) of albendazole/kg of body weight each day for 14 days, there were no gross or microscopic lesions attributable to the drug. PMID:666077

  12. Determination of Albendazole and Metabolites in Silkworm Bombyx mori Hemolymph by Ultrafast Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometry

    PubMed Central

    Li, Li; Xing, Dong-Xu; Li, Qing-Rong; Xiao, Yang; Ye, Ming-Qiang; Yang, Qiong

    2014-01-01

    Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905–0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%–103.83% for ABZ, 66.51%–108.51% for ABZSO, 96.85%–105.6% for ABZSO2 and 96.46%–106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time. PMID:25255321

  13. Albendazole, a broad-spectrum anthelmintic, in the treatment of intestinal nematode and cestode infection: a multicenter study in 480 patients.

    PubMed

    Jagota, S C

    1986-01-01

    The anthelmintic activity of and patient tolerance to albendazole, a broad-spectrum anthelmintic, were studied in a multicenter trial involving 480 patients ranging in age from 2 to 60 years. The patients had single or mixed infections caused by pinworms, roundworms, hookworms, whipworms, threadworms, or tapeworms. The stools were examined by the direct method, and ova were counted by means of the Kato-Katz technique. A Graham-Scotch test was also done in patients infected with Enterobius vermicularis. Most patients received a single 400-mg dose of albendazole; adults were given two tablets, and children were given a 2% suspension. All patients with Hymenolepis nana and about half of those with Taenia infections were treated for three successive days. Patients were carefully evaluated before and after treatment to assess the efficacy and safety of the drug. After a single dose of albendazole, the cure rate was 95.3% in ascariasis, 92.2% in ancylostomiasis, 90.5% in trichuriasis, 64.9% in taeniasis, and 100% in enterobiasis. Among patients receiving 400 mg of albendazole for three days, the cure rate was 63.4% in hymenolepiasis and 86.1% in taeniasis. The drug was well tolerated, and no significant side effects were reported. PMID:3516398

  14. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

    PubMed

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-02-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

  15. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia

    PubMed Central

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-01-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from −1900% to 100%, 99% to 100%, −167% to 100%, −467% to 89%, and −200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

  16. Albendazole sulphoxide enantiomers in pregnant rats' embryo concentrations and developmental toxicity.

    PubMed

    Capece, B P S; Navarro, M; Arcalis, T; Castells, G; Toribio, L; Perez, F; Carretero, A; Ruberte, J; Arboix, M; Cristòfol, C

    2003-05-01

    Three single oral doses (8.5, 10, and 14 mg/kg) of a racemic formulation of albendazole sulphoxide (ABZSO) were administered to pregnant rats on day 10 of gestation. Mother plasma and embryo concentrations of ABZSO enantiomers and albendazole sulphone (ABZSO(2)) were determined 9 h after administration. The (-)-ABZSO enantiomer showed higher peak concentrations in both maternal plasma and embryo than the (+) enantiomer. An increase in embryo concentrations of ABZSO enantiomers and ABZSO(2) was only observed when dose rose to 14 mg/kg. There was an increase in resorption when the dose increased, but significant differences were only found in the higher dose group when compared with the other groups. The incidence of external and skeletal malformations (mostly of the tail, vertebrae and ribs) rose significantly in the 10 mg/kg group, producing almost 20% and 90% of malformed fetuses, respectively, and gross external and skeletal abnormalities in the thoracic region and limbs were also found. PMID:12672373

  17. Single-Dose Doxycycline for Cholera

    PubMed Central

    Sack, David A.; Islam, Sirajul; Rabbani, Hassan; Islam, Asma

    1978-01-01

    To determine the efficacy of single-dose doxycycline in the treatment of cholera, we carried out a randomized prospective trial in 65 patients. Treatment consisted of either a single dose of 200 mg of doxycycline (or 4 mg/kg in patients less than 15 years old) or multiple doses of doxycycline, 500 mg over 4 days (or 10 mg/kg in patients less than 15 years old). There were no differences between the groups in the volumes of intravenous fluid required, volumes of diarrheal stool, or durations of diarrhea. The mean duration of positive stool cultures for Vibrio cholerae was similar for the two groups, although in both groups several patients continued to excrete Vibrios in the stool for more than 3 days. Blood levels of antibiotic demonstrated that the doxycycline was absorbed in spite of the rapid transit time associated with severe diarrhea. These results suggest that although tetracycline remains the drug of choice for cholera, doxycycline is a reasonable alternative, and that a single dose of 200 mg (4 mg/kg in children) is effective clinically. PMID:708024

  18. Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

    PubMed Central

    Humphries, Debbie; Simms, Benjamin T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-01-01

    Children (n = 812) 6–11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564

  19. Hookworm infection among school age children in Kintampo north municipality, Ghana: nutritional risk factors and response to albendazole treatment.

    PubMed

    Humphries, Debbie; Simms, Benjamin T; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-09-01

    Children (n = 812) 6-11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564

  20. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial

    PubMed Central

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-01-01

    Summary Background Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10–2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87–2·38, p=0·151

  1. In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium.

    PubMed

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E; Cass, Quezia B

    2013-02-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (-)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (-)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole. PMID:23229490

  2. In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-(R)-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

    PubMed Central

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H.; Cass, Quezia B.

    2013-01-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (−)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (−)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (−)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole. PMID:23229490

  3. Single dose dipyrone for acute postoperative pain

    PubMed Central

    Derry, Sheena; Faura, Clara; Edwards, Jayne; McQuay, Henry J; Moore, R Andrew

    2014-01-01

    Background Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. Objectives To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. Search methods The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Selection criteria Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls. Over 70% of participants

  4. Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru.

    PubMed

    Juan, Jave Ortiz; Lopez Chegne, Nicholas; Gargala, Gilles; Favennec, Loic

    2002-01-01

    Three randomized clinical studies were conducted in 2000 to evaluate the efficacy of nitazoxanide paediatric suspension compared to albendazole in the treatment of ascariasis and trichuriasis and praziquantel in the treatment of hymenolepiasis in children from Cajamarca, Peru. Nitazoxanide was administered at a dose of 100 mg (age 1-3 years) or 200 mg (age 4-11 years) twice daily for 3 days, albendazole as a 400-mg single dose and praziquantel as a 25-mg/kg single dose. Post-treatment parasitological examinations were carried out on 3 faecal samples, each collected on a different day between 21 and 30 days following initiation of treatment. Nitazoxanide cured 89% (25/28), 89% (16/18) and 82% (32/39) of the cases of ascariasis, trichuriasis and hymenolepiasis respectively compared with 91% (32/35), 58% (11/19) and 96% (47/49) for the comparator drugs. Each of the drugs produced egg reduction rates in excess of 98%. There were no significant adverse events or abnormalities in haematology or clinical chemistry values or urinalysis. PMID:12055813

  5. Placental transfer of albendazole sulphoxide enantiomers in sheep.

    PubMed

    Capece, B P S; Pérez, R; Andaluz, A; Pérez, F; Garcia, F; Castells, G; Arboix, M; Cristòfol, C

    2002-03-01

    Albendazole sulphoxide (ABZSO) is an anthelmintic drug used in veterinary practice. Its molecule has a chiral centre in the sulphur atom and racemic formulations are always used. The kinetics of the ABZSO enantiomers in the last third of pregnancy in ewes, and the placental transfer to the fetus, were studied after a single-dose oral administration (7.5 mg/kg) of a racemic formulation. In mothers, the area under the plasma concentration-time curve (AUC) and C(max) values of (+)-ABZSO (42.4+/-10.5 microg/mL and 1.9+/-0.4 microg/mL, respectively) were higher than those of (-)-ABZSO (15.3+/-5.1 microg/mL and 1.0+/-0.3 microg/mL). The MRT values were 17.0+/-1.6 h for (+)-ABZSO and 13.1+/-1.8 h for (-)-ABZSO. Similar kinetic parameters were obtained in the fetus for both enantiomers, but the fetal concentrations were lower compared with values for the dam. The AUC ratio between (-)-ABZSO/(+)-ABZSO in the dam was 0.36 and in the fetuses 0.64, indicating a higher impairment for the (+)-enantiomer in its placental transfer to the fetus. PMID:12093190

  6. [EXPERIENCE IN TREATING HELMINTHISM WITH MICRONIZED ALBENDAZOLE (GELMODOL)].

    PubMed

    Zavoikin, V D; Tumolskaya, N I; Mazmanyan, M V; Zelya, O P; Tikhonova, D V

    2015-01-01

    The paper gives the results of treatment with micronized albendazole (Gelmodol-BM, World Medicine, UK) in 87 patients of the Department of Medical Parasitology and Tropical Diseases, Clinical and Diagnostic Center, Clinical Center, I.M.Sechenov First Moscow State Medical University. Thirty-two patients with echinococcosis 8 with alveococcosis (including 4 inoperable patients), 10 with ascariasis, 10 with toxocariasis, 15 with enterobiasis, and 12 people diagnosed with larva migrans were treated in 2013-2014. The drug's routine doses and dosage regimens were used. Albendazole (Gelmodol, World Medicine, UK) showed a high efficacy with good tolerability, which is highly competitive with that of the drugs manufactured by IPCA Laboratories Ltd., India (such as nemozole). Both medicaments above-mentioned may be successfully used in the treatment of many helminthisms. PMID:26827590

  7. Single dose NTBC-treatment of hereditary tyrosinemia type I.

    PubMed

    Schlune, A; Thimm, E; Herebian, D; Spiekerkoetter, U

    2012-09-01

    NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3cyclohexanedione) is the mainstay of treatment in tyrosinemia type 1 (HT 1). The current recommendation is to divide the total daily dose of NTBC into two doses. We monitored the plasma NTBC concentrations in a series of seven patients who were changed from multiple divided doses to a single daily dose of NTBC. Two additional patients were started on a single daily dose of NTBC after the diagnosis of HT 1 was established. In three patients, NTBC kinetics were performed over 6 and 24 hours, respectively. The use of multiple divided doses or a single daily dose did not significantly affect plasma NTBC concentrations or the mean daily dose needed to attain therapeutic plasma NTBC concentrations. Moreover, kinetic studies demonstrated that plasma NTBC concentrations were completely stable over a period of 24 hours with a single dose regimen, as expected given the known NTBC plasma half life of 54 hours. Although these preliminary results need to be confirmed in more patients, our findings show that administration of NTBC in a single daily dose may be as effective as a multiple-dose regimen in reaching therapeutic plasma NTBC concentrations and suppressing succinylacetone formation in patients with HT 1. In fact, single dose treatment may increase patients' compliance with the drug treatment and improve metabolic control. PMID:22307209

  8. Comparing single and cumulative dosing procedures in human triazolam discriminators.

    PubMed Central

    Smith, B J; Bickel, W K

    1999-01-01

    This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination. PMID:10344022

  9. Anthelmintic activity of albendazole against gastrointestinal nematodes in calves.

    PubMed

    Benz, G W; Ernst, J V

    1977-09-01

    Anthelmintic activities of albendazole were evaluated in a controlled experiment. Forty calves experimentally infected with gastrointestinal nematodes were allotted to 4 groups. Calves in group 1 were used as nonmedicated controls; calves in groups 2, 3, and 4 were given (by oral route) a suspension containing albendazole at dose concentrations of 2.5, 5.0, and 7.5 mg/kg of body weight on the 35th day after administration of infective nematode larvae. In groups 2, 3, and 4 calves, average overall reductions (based on geometric means) were 77.1, 93.6, and 98.1%, respectively. These reductions were highly significant (P less than 0.01) in calves given doses of 5.0 and 7.5 mg/kg, and were significant (P less than 0.05) in calves given the 2.5-mg/kg dose. Ostertagia ostertagi, Trichostrongylus axei, Cooperia onchophora, Cooperia punctata, and Oesophagostomum radiatum removals at the 5.0- and 7.5-mg/kg dose levels were all highly significant (P less than 0.01); whereas, removals of Haemonchus contortus were not significant, even at the 7.5-mg/kg dose level. PMID:921039

  10. The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji

    PubMed Central

    Kimura, Eisaku

    2011-01-01

    Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission. From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced “beyond-filariasis” benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 µg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.) The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was

  11. The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji.

    PubMed

    Kimura, Eisaku

    2011-03-01

    Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced "beyond-filariasis" benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites.The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 µg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.)The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was the

  12. Albendazole

    MedlinePlus

    ... to treat neurocysticercosis (infection caused by the pork tapeworm in the muscles, brain, and eyes that may ... cystic hydatid disease (infection caused by the dog tapeworm in the liver, lung, and lining of the ...

  13. Albendazole

    MedlinePlus

    ... threadworm, whipworm, pinworm, flukes, and other parasites (a plant or animal that lives within another living organism ... it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away ...

  14. Development of bone marrow toxicosis after albendazole administration in a dog and cat.

    PubMed

    Stokol, T; Randolph, J F; Nachbar, S; Rodi, C; Barr, S C

    1997-06-15

    Bone marrow toxicosis was detected in a dog and cat following albendazole administration. Both animals were admitted with pancytopenia. In the dog, pancytopenia was attributed to severe panmarrow hypoplasia, whereas the cat had hypoplasia of erythroid and megakaryocytic series, but with a left-shifted granulocytic hyperplasia. Results of cytologic examination of bone marrow from both animals were compatible with acute injury. Both animals had been treated with albendazole for giardiasis prior to the onset of clinical signs. Bone marrow toxicosis was attributed to albendazole administration for the following reasons: this was the only or most recent drug administered, other causes of bone marrow toxicosis were not found, and both animals recovered rapidly with supportive care that consisted of fluid and antibiotic administration. Albendazole induced toxicosis appeared to be dose related in the dog and idiosyncratic in the cat. On the basis of the findings in this report, there is a potential for the development of albendazole induced bone marrow toxicosis in dogs and cats; therefore, veterinarians should exercise caution when using this drug. PMID:9187723

  15. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

    PubMed Central

    Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

    2016-01-01

    , there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence). In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials). Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Authors' conclusions Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole. Ivermectin versus benzimidazoles for treating Strongyloides stercoralis infection What is strongyloides infection and how might ivermectin work Strongyloides stercoralis is a parasite that lives in the gut of infected people. The infection is not serious for most people, but it can be fatal in people with immune deficiency. People become infected when they come in contact with soil or water contaminated with infectious worms. The chronic infection usually causes skin rash, vomiting, diarrhoea, and constipation, and respiratory problems, such as asthma-like illness. This disease may be treated with ivermectin or albendazole or thiabendazole. We wanted to know if ivermectin was better or worse than the other alternative therapies. What the research says We reviewed the evidence about the effect of ivermectin compared with albendazole and thiabendazole. After searching for relevant trials up to August 2015, we included seven randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations (Africa

  16. Single-dose versus multi-dose vaccine vials for immunization programmes in developing countries.

    PubMed Central

    Drain, Paul K.; Nelson, Carib M.; Lloyd, John S.

    2003-01-01

    Excessive vaccine wastage and safety concerns have prompted the international health community to develop and supply vaccines in formats other than the standard multi-dose vial. This article presents a programmatic and economic comparison of the major differences between the multi-dose vials and single-dose formats used for immunization services in developing countries. Multi-dose vials, in general, sell at a lower per-dose price and occupy less cold-chain capacity than single-dose formats. However, higher wastage rates may offset these benefits, especially for more expensive vaccines. Single-dose formats offer several important programmatic benefits, such as increased vaccination opportunities and improved vaccine safety. One single-dose format, the prefilled auto-disable (AD) device, provides additional injection safety and convenience features because it physically combines the vaccine and AD syringe. Selecting the appropriate vaccine presentation will depend on many factors. However, multi-dose vials are likely to be most appropriate for cheaper vaccines and in settings where cold-chain storage capacity is restricted. Single-dose formats will be most appropriate for more expensive vaccines and where there are problems with unsafe injection practices. Prefilled AD injection devices will be particularly useful in expanding outreach services while eliminating the possibility of needle reuse. PMID:14758432

  17. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    ERIC Educational Resources Information Center

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  18. Improving bioavailability and anthelmintic activity of albendazole by preparing albendazole-cyclodextrin complexes.

    PubMed

    García-Rodriguez, J J; Torrado, J; Bolás, F

    2001-06-01

    The bioavailability and anthelmintic activity of albendazole-cyclodextrin complexes (ABZ-CDC) compared to albendazole suspensions in carboxymethylcellulose (ABZ-CMC) was assessed in a mouse model for Trichinella infections. Swiss CD-1 mice experimentally infected with T. spiralis were treated with both formulations against enteral (adult worms) and parenteral (migrating and encysted larvae). Oral bioavailability was assessed in age matched mice treated with 50 mg/kg of both formulations. The anthelmintic effects and plasma concentration of the active metabolite albendazole-sulphoxide (ABZSO) enantiomer (-) were significantly increased following administration of ABZ-CDC in relation to ABZ-CMC. PMID:11484352

  19. Single-dose oral guanidinoacetic acid exhibits dose-dependent pharmacokinetics in healthy volunteers.

    PubMed

    Ostojic, Sergej M; Vojvodic-Ostojic, Aleksandra

    2015-03-01

    Guanidinoacetic acid (GAA), the natural precursor of creatine, has potential as a dietary supplement for human nutrition, yet no data are available regarding its dose-dependent pharmacokinetic (PK) behavior. We hypothesized that a single dose of orally administered GAA exhibited dose-dependent PK behavior in healthy volunteers. Forty-eight young adults were enrolled in a randomized, placebo-controlled, double-blind, parallel-group trial to receive single oral doses of GAA (1.2, 2.4, and 4.8 g) or a placebo. Pharmacokinetic metrics for plasma GAA and creatine were assessed immediately before (0 hours) and at 1, 2, 4, 6, 8, 12, and 24 hours after GAA ingestion. The lag time appeared to be similar after the bolus ingestion of GAA (0.14 ± 0.17 hours for low-dose GAA, 0.31 ± 0.18 hours for medium-dose GAA, and 0.38 ± 0.32 hours for high-dose GAA; P = .05). An increase in the area under the concentration-time curve for plasma GAA was found for the dose range tested, with 2.4- and 9.3-fold increases in the area under the concentration-time curve for every 2-fold increase in the GAA dose (P < .0001). No differences were found for elimination half-time between the low-dose and medium-dose groups (<1.75 hours), whereas the elimination half-time was significantly longer (>2.1 hours) for the high-dose GAA regimen (P = .001). The volume of distribution was affected by the dosage of GAA applied (102.6 ± 17.3 L for low-dose GAA, 97.5 ± 15.7 L for medium-dose GAA, and 61.1 ± 12.7 L for high-dose GAA; P < .0001). Ingestion of GAA elevated plasma creatine by 80%, 116%, and 293% compared with the placebo for the 1.2, 2.4, and 4.8 g doses, respectively (P < .0001). Guanidinoacetic acid single-dose PK metrics were nonlinear with respect to dose size. Across the dose range of 1.2 to 4.8 g, systemic exposure to GAA increased in a greater than dose-proportional manner. PMID:25622538

  20. Single oral dose proportionality pharmacokinetics of almitrine bismesylate in humans.

    PubMed

    Stavchansky, S; Doluisio, J T; Macleod, C M; Szalkowski, M B; Bachand, R T; Heilman, R; Sebree, T B; Geary, R S

    1989-01-01

    A single-blind study was conducted in 10 healthy male subjects. Each subject was tested with four single oral doses of capsules containing 25, 50, 100, 200mg almitrine bismesylate and one dose of placebo. Blood samples were drawn as a function of time and the concentration of almitrine in plasma was determined by gas chromatography utilizing nitrogen-phosphorus detection. Linear regression analysis of the data suggested that a deviation from linearity existed between the area under the plasma concentration time curves and the dose (R = 0.96). Linear analysis of the individual data indicates that a slight negative deviation from linearity is apparent for the 200 mg dose. The same trend was observed for the mean maximum almitrine plasma concentration, Cmax, which ranged from 38.9 +/- 11.8 to 286.2 +/- 99.1 ng ml-1 for the 25 and 200 mg dose, respectively. The time to peak was relatively constant regardless of the administered dose and ranged from 2.4 +/- 0.5 h to 2.8 +/- 0.8 h. Good agreement was obtained between the observed bioavailability parameters and those predicted from the nonlinear fit of the data. Further kinetic analysis of the data revealed mean total body clearance over fraction of dose absorbed ranging from 268.2 +/- 132.8 to 436.4 +/- 191.4 ml min-1 for doses 50 and 200mg, respectively. PMID:2566337

  1. A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia

    PubMed Central

    Bray, Walter M.; White, Pamela M.; Ruybal, Jordan; Lokey, R. Scott; Debec, Alain; Sullivan, William

    2012-01-01

    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

  2. Placental and fetal toxicity of albendazole sulphoxide in Wistar rats.

    PubMed

    Teruel, Miriam T; Felipe, Antonio E; Solana, Hugo D; Sallovitz, Juan M; Lanusse, Carlos E

    2003-06-01

    This work characterized the effects of albendazole sulphoxide (ABZSO) on placental and fetal parameters in Wistar rats on day 20 of gestation. ABZSO was fed in laboratory chow at 0, 2.5, 5, 10, 20 or 30 mg/kg/d from day 6 to 15 of gestation to pregnant rats. Data of resorptions, placental and fetal characteristics and fetal skeletal malformations were recorded. Resorption percentages in the 20 and 30 mg/kg/d groups were significantly higher compared to the control group. Placentas of ABZSO-treated rats had lower weight and smaller size than untreated rats. The fetal weight and size were lower in the 5 mg/kg/d dose compared to no treatment. In the 5, 10 and 20 mg/kg/d groups, reductions in ossification process were observed. ABZSO induced malformations and/or fetal death when orally administered to pregnant rats. This data contributes to characterization of the reproductive toxicity of ABZSO, the main active metabolite of albendazole. PMID:12776788

  3. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  4. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  5. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  6. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  7. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  8. Disposition of netobimin, albendazole, and its metabolites in the pregnant rat: developmental toxicity.

    PubMed

    Cristòfol, C; Navarro, M; Franquelo, C; Valladares, J E; Carretero, A; Ruberte, J; Arboix, M

    1997-05-01

    Netobimin (NTB), a benzimidazole prodrug with a good anthelmintic spectrum, was administered orally to female rats at a dose of 59.5 mg NTB/kg, to study its pharmacokinetic behavior and the disposition of its most important metabolites, albendazole (ABZ), albendazole sulfoxide (ABZSO), and albendazole sulfone (ABZSO2). ABZ was found in plasma after 6 hr. Peak plasma concentrations (Cmax) and areas under curves (AUC) of ABZSO were eight- and fourfold higher, respectively, than those of ABZSO2. To study NTB disposition in pregnant rats, three different drug doses (50, 59.5, and 70.7 mg/kg) were given. No significant differences were found between plasma concentrations for each metabolite at the three doses studied. Only ABZ concentrations rose slightly as dose increased. ABZ, ABZSO, and ABZSO2 were found in amniotic sacs and embryos at concentrations that were higher than plasma at the same times. The fetuses obtained after administration of each of the doses of NTB were studied to detect developmental toxicity. A significant correlation was found between rate of developmental toxicity and metabolite concentration. ABZSO embryo concentrations could be the main factor accounting for toxicity. PMID:9169069

  9. Patterns of geohelminth infection, impact of albendazole treatment and re-infection after treatment in schoolchildren from rural KwaZulu-Natal/South-Africa

    PubMed Central

    Saathoff, Elmar; Olsen, Annette; Kvalsvig, Jane D; Appleton, Chris C

    2004-01-01

    Background Geohelminth infection is a major health problem of children from rural areas of developing countries. In an attempt to reduce this burden, the Department of Health of the province of KwaZulu-Natal (KZN) established in 1998 a programme for helminth control that aimed at regularly treating primary school children for schistosomiasis and intestinal helminths. This article describes the baseline situation and the effect of treatment on geohelminth infection in a rural part of the province. Methods Grade 3 schoolchildren from Maputaland in northern KZN were examined for infections with hookworm, Ascaris lumbricoides, and Trichuris trichiura, treated twice with 400 mg albendazole and re-examined several times over one year after the first treatment in order to assess the impact of treatment and patterns of infection and re-infection. Results The hookworm prevalence in the study population (83.2%) was considerably higher than in other parts of the province whereas T. trichiura and especially A. lumbricoides prevalences (57.2 and 19.4%, respectively) were much lower than elsewhere on the KZN coastal plain. Single dose treatment with albendazole was very effective against hookworm and A. lumbricoides with cure rates (CR) of 78.8 and 96.4% and egg reduction rates (ERR) of 93.2 and 97.7%, respectively. It was exceptionally ineffective against T. trichiura (CR = 12.7%, ERR = 24.8%). Re-infection with hookworm and A. lumbricoides over 29 weeks after treatment was considerable but still well below pre-treatment levels. Conclusion High geohelminth prevalences and re-infection rates in the study population confirm the need for regular treatment of primary school children in the area. The low effectiveness of single course albendazole treatment against T. trichiura infection however demands consideration of alternative treatment approaches. PMID:15310401

  10. Replacing the Measles Ten-Dose Vaccine Presentation with the Single-Dose Presentation in Thailand

    PubMed Central

    Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Chen, Sheng-I; Bailey, Rachel R.; Wiringa, Ann E.; Wateska, Angela R.; Jana, Anirban; Van Panhuis, Willem G.; Burke, Donald S.

    2011-01-01

    Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand is currently considering) and a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations’ storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage. PMID:21439313

  11. Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

    PubMed Central

    Lockman, S.; Hughes, M.D.; McIntyre, J.; Zheng, Y.; Chipato, T.; Conradie, F.; Sawe, F.; Asmelash, A.; Hosseinipour, M.C.; Mohapi, L.; Stringer, E.; Mngqibisa, R.; Siika, A.; Atwine, D.; Hakim, J.; Shaffer, D.; Kanyama, C.; Wools-Kaloustian, K.; Salata, R.A.; Hogg, E.; Alston-Smith, B.; Walawander, A.; Purcelle-Smith, E.; Eshleman, S.; Rooney, J.; Rahim, S.; Mellors, J.W.; Schooley, R.T.; Currier, J.S.

    2010-01-01

    BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National

  12. Single dose oral diclofenac for acute postoperative pain in adults

    PubMed Central

    Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours

  13. Single oral dose safety of D-allulose in dogs

    PubMed Central

    NISHII, Naohito; NOMIZO, Toru; TAKASHIMA, Satoshi; MATSUBARA, Tatsuya; TOKUDA, Masaaki; KITAGAWA, Hitoshi

    2016-01-01

    Healthy dogs were administered acute oral doses of D-allulose (also called D-psicose) to evaluate its toxicity. Six dogs received oral doses of either a placebo or D-allulose solution (1 and 4 g/kg) on three different study days. One dog experienced vomiting, and five dogs showed transient diarrhea when 4 g/kg of D-allulose was administered. All dogs were active and had a good appetite throughout the study period. Blood glucose concentration slightly decreased without a rise in plasma insulin concentration 2 hr after D-allulose administration. Plasma alkaline phosphatase activities showed a mild increase between 12 and 48 hr after D-allulose administration. These data suggested that a single oral dose of D-allulose does not show severe toxicity in dogs. PMID:26972334

  14. Single and multiple dose pharmacokinetics of etizolam in healthy subjects.

    PubMed

    Fracasso, C; Confalonieri, S; Garattini, S; Caccia, S

    1991-01-01

    The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, alpha-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines. PMID:2065698

  15. Single-dose kinetics of mefloquine in Brazilian male subjects

    PubMed Central

    de Souza, J. M.; Heizmann, P.; Schwartz, D. E.

    1987-01-01

    Ten male subjects from a region of the state of Pará, Brazil, where malaria is endemic received a single oral dose of 1000 mg mefloquine. The plasma levels of the drug and of its metabolite, 2,8-bis(trifluoromethyl)-4-quinolinecarboxylic acid, were determined densitometrically on thin-layer chromatography plates. The pharmacokinetic parameters obtained fell well within the range of values reported previously for Africans and Caucasians. PMID:3499250

  16. Single-Dose Radiation-Induced Oral Mucositis Mouse Model

    PubMed Central

    Maria, Osama Muhammad; Syme, Alasdair; Eliopoulos, Nicoletta; Muanza, Thierry

    2016-01-01

    The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23 g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25 Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10 μm, respectively, compared to 200 μm in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25 Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25 Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1 mL of 0.9% saline/6 h for 24 h yielded a 100% survival only with 18 Gy self-resolved RIOM, which had 5.6 ± 0.3 days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival. PMID:27446800

  17. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

    NASA Astrophysics Data System (ADS)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  18. Critical anthelmintic trials in ponies with four benzimidazoles: mebendazole, cambendazole, fenbendazole, and albendazole.

    PubMed

    Colglazier, M L; Enzie, F D; Kates, K C

    1977-08-01

    The comparative efficacy of four benzimidazoles against gastrointestinal parasites of ponies was evaluated by the critical test method. Mebendazole (8.8 mg/kg), cambendazole (20 mg/kg), fenbendazole (5 mg/kg), and albendazole (2.5 and 5 mg/kg) given in single oral doses were highly effective against adult large strongylids (Strongylus vulgaris, S. endentatus, S. equinus) and adult small strongylids (genera identified in order of frequency: Cylicostephanus, Cylicocyclus, Cyathostomum, Triodontophorus, Poteriostomum, Oesophagodontus, Cylicodontophorus, Gyalocephalus, and Craterostomum). Limited data indicated that all benzimidazoles were completely effective against adult Oxyuris equi and 95 to 100% effective against the 4th stage larvae. There was activity also against the large roundworm, Parascaris equorum, although the low levels of infection and skew distribution among the test animals did not permit a definitive determination of efficacy. Habronema muscae, Draschia megastoma, and Trichostrongylus axei were found in digests of the stomach but none were recovered in the feces after treatment; percent efficacy for these species was not calculated. None of the benzimidazoles showed activity against stomach bots, Gasterophilus spp., and tapeworms, Anoplocephala spp. nor against immature large and small strongylids outside the lumen of the digestive tract. PMID:886410

  19. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

    PubMed

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

    2011-05-01

    an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments. PMID:21525648

  20. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

    PubMed Central

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

    2011-01-01

    combined with an improved understanding of the effects of dose and dose rate will aid single-particle cryo-electron microscopists to have better control of the outcome of their experiments. PMID:21525648

  1. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults

    PubMed Central

    Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on ‘Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain’. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. Objectives To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Main results Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at

  2. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

    PubMed Central

    Vally, H; Thompson, P

    2001-01-01

    BACKGROUND—Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employed to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites.
METHODS—In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine.
RESULTS—Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV1) (>15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV1 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV1, peak expiratory flow (PEF), mid phase forced expiratory

  3. Equine verminous arteritis; efficiency and speed of larvicidal acitivty as influenced by dosage of albendazole.

    PubMed

    Georgi, J R; Rendano, V T; King, J M; Bianchi, D G; Theodorides, V J

    1980-04-01

    Albendazole was effective in destroying Strongylus vulgaris larvae in verminous lesions of the cranial mesenteric artery when administered as a 20% suspension by stomach tube to ponies. Fifty mg/kg body weight administered twice a day for 2 days caused death and gradual disintegration of larvae over a period of 3 to 6 weeks with mild toxic signs appearing in 3 of 11 ponies. Higher total doses of albendazole (50 mg/kg twice a day for 4 days and 25 mg/kg three times a day for 5 days) lead to more rapid disintegration of the larvae but fatal toxicity was observed in 3 of 6 ponies so treated. In all cases, resolution of verminous arterial lesions was delayed until larva remains had disappeared from the lesions. A non-parametric analysis was applied to combined radiographic, pathologic and parasitologic observations and data for testing their statistical significance PMID:7408495

  4. Trichuris suis and Oesophagostomum dentatum Show Different Sensitivity and Accumulation of Fenbendazole, Albendazole and Levamisole In Vitro

    PubMed Central

    Hansen, Tina V. A.; Nejsum, Peter; Friis, Christian; Olsen, Annette; Thamsborg, Stig Milan

    2014-01-01

    Background The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known. Methodology We studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species. Principal findings The motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6–17.2%) as compared to O. dentatum (0.8–0.9%). Conclusion/Significance The general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum. PMID:24699263

  5. Single dose oral ibuprofen for acute postoperative pain in adults

    PubMed Central

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This review updates a 1999 Cochrane review showing that ibuprofen at various doses was effective in postoperative pain in single dose studies designed to demonstrate analgesic efficacy. New studies have since been published. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory (NSAID) analgesics both by prescription and as an over-the-counter medicine. Ibuprofen is used for acute and chronic painful conditions. Objectives To assess analgesic efficacy of ibuprofen in single oral doses for moderate and severe postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ibuprofen (any formulation) in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Seventy-two studies compared ibuprofen and placebo (9186 participants). Studies were predominantly of high reporting quality, and the bulk of the information concerned ibuprofen 200 mg and 400 mg. For at least 50% pain relief compared with placebo the NNT for ibuprofen 200 mg (2690 participants) was 2.7 (2.5 to 3.0) and for ibuprofen 400 mg (6475 participants) it was 2.5 (2.4 to 2.6). The proportion with at least 50% pain relief was 46% with 200 mg and 54% with 400 mg. Remedication within 6 hours was less

  6. Neurocysticercosis with Diplopia Responds Well to Albendazole.

    PubMed

    Sato, Akihiro; Nakamura, Itaru; Fujita, Hiroaki; Fukushima, Shinji; Mizuno, Yasutaka; Fujii, Takeshi; Matsumoto, Tetsuya

    2016-01-01

    We report a case of neurocysticercosis concurrent with taeniasis in a 31-year-old woman. The patient presented with a headache and diplopia. Oculomotor disturbances with a left adduction deficit were observed. Fundoscopy revealed papilledema. Additionally, computed tomography of the brain revealed more than 20 small cysts within the parenchyma, most of which were associated with ring enhancement. Moreover, serum antibody testing (Western blotting) for Taenia solium-cysticerci was positive. The patient received albendazole and corticosteroids, and progressive resolution of the neurological symptoms and papilledema was observed starting approximately three days after administration. This patient has been asymptomatic for more than one year. PMID:27150884

  7. Cardiac Safety of Diclofenac at a Single Dose in Ram

    PubMed Central

    Er, Ayse; Dik, Burak

    2013-01-01

    Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5 mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), and muscular (creatine kinase) damage markers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep. PMID:24228015

  8. Pharmacokinetics of single-dose oral ponazuril in weanling goats.

    PubMed

    Love, D; Gibbons, P; Fajt, V; Jones, M

    2016-06-01

    Ponazuril (toltrazuril sulfone) is a triazine antiprotozoal agent that targets apicomplexan organisms. Ponazuril may have clinical application in the treatment of clinical coccidiosis due to Eimeria species in goats, along with other protozoal infections. To evaluate the absorption, distribution and elimination characteristics of ponazuril in goats, a sensitive, validated high-pressure liquid chromatography and mass spectroscopy method for ponazuril in caprine plasma was developed. After a single oral dose of ponazuril at 10 mg/kg, plasma samples from seven weanling goats were collected and assayed. Plasma concentrations of ponazuril in the goats peaked at 36 ± 13 h post drug administration at a concentration of 9 ± 2 μg/mL. Concentrations declined to an average of 4.2 ± 0.8 μg/mL after 168 h with an average elimination half-life of 129 ± 72 h post drug administration. This study shows that ponazuril is relatively well absorbed after a single oral dose in goats. Efficacy trials are underway to determine clinical efficacy of ponazuril in the treatment of clinical coccidiosis in goats at 10 mg/kg dosage. PMID:26542450

  9. [Clinical study of the efficacy of albendazole treatment in human hydatidosis].

    PubMed

    Rădulescu, S; Angelescu, N; Horvat, T; Lazăr, L; Creţu, C; Popa, L; Filiu, P; Ene, V; Burcoş, T; Ifrim, S; Popa, G

    1997-01-01

    A follow-up study of Albendazol effectiveness therapy in human hydatid diseases was carry out using WHO methodology. Albendazole was given at a dose of 10 mg/Kg body/day in cycles of 28 days separated by 14 days without treatment. The efficacy of chemotherapy was evaluated by clinical improvement and changes in the cyst's morphology (detachment and collapse of the cyst membrane and increased density of the cyst fluid). We performed this study in 134 patients with hydatidosis: 17 patients with pre and post surgery treatment, 50 patients with post surgery treatment and 67 patients with chemotherapy only. Albendazole was effective in the hydatid disease; the patients with complex chemotherapy treatment did not report any secondary hydatidosis during the follow-up period (max. 2 years); the patients with exclusive chemotherapy reported 79% successful response, only 21% of them remained with unchanged cyst's size, but with modified internal structure. The therapeutic response depends of the cyst's size and its visceral site. PMID:9462951

  10. Single dose oral lumiracoxib for postoperative pain in adults

    PubMed Central

    Roy, Yvonne M; Derry, Sheena; Moore, R Andrew

    2014-01-01

    Background Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors were developed to avoid COX-1-related gastrointestinal (GI) problems while maintaining the analgesic and anti-inflammatory activity of traditional non-steriodal anti-inflammatory drugs (NSAIDs). Objectives To review the analgesic efficacy, duration of analgesia, and adverse effects of a single oral dose of lumiracoxib for moderate to severe postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, and EMBASE to February 2010. Selection criteria Single oral dose, randomised, double-blind, placebo-controlled trials of lumiracoxib for relief of established moderate to severe postoperative pain in adults. Data collection and analysis Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR 6) was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Numbers of participants using rescue medication, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results In this updated review four studies met the inclusion criteria. In total 366 participants were treated with lumiracoxib 400 mg, 51 with lumiracoxib 100 mg, and 212 with placebo. Active comparators were naproxen 500 mg, rofecoxib 50 mg, celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 400 mg. With lumiracoxib 400 mg 50% of participants had at least 50% pain relief over six hours, compared with 8% given placebo; RB 6.9 (95% CI 4.1 to 12), NNT 2.4 (2.1 to 2.8). Median time to onset of analgesia was shorter for lumiracoxib 400 mg (0.6 to 1.5 hours) than

  11. Single dose oral piroxicam for acute postoperative pain

    PubMed Central

    Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

  12. Albendazole sulfoxide enantiomers: preparative chiral separation and absolute stereochemistry.

    PubMed

    Lourenço, Tiago C; Batista, João M; Furlan, Maysa; He, Yanan; Nafie, Laurence A; Santana, Cesar C; Cass, Quezia B

    2012-03-23

    The enantiomeric separation of albendazole sulfoxide was carried out by simulated moving bed chromatography with variable zones (VARICOL). An overall recovery of 97% was achieved and enantiomeric ratios of 99.5% for raffinate and 99.0% for extract were attained. A total of 880 mg of (+)-albendazol sulfoxide and 930 mg of its antipode were collected after 55 cycles or 11 h of process, resulting in a mass rate of 2 g/day. Furthermore the absolute configuration of the enantiopure compounds was determined for the first time by vibrational circular dichroism (VCD) with the aid of theoretical calculations as (-)-(S) and (+)-(R)-albendazole sulfoxide. PMID:22341660

  13. 21 CFR 520.45a - Albendazole suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver...) body weight (10 mg/kilogram (kg)) as a single oral dose using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver flukes (Fasciola hepatica); heads and segments...

  14. 21 CFR 520.45a - Albendazole suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver...) body weight (10 mg/kilogram (kg)) as a single oral dose using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver flukes (Fasciola hepatica); heads and segments...

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

    PubMed

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

    2016-09-01

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

  16. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    PubMed

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration. PMID:26582164

  17. Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

    SciTech Connect

    Kim, Yeon-Joo; Cho, Kwan Ho; Kim, Joo-Young; Lim, Young Kyung; Min, Hye Sook; Lee, Sang Hyun; Kim, Ho Jin; Gwak, Ho Shin; Yoo, Heon; Lee, Seung Hoon

    2011-10-01

    Purpose: To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results: With a median follow-up period of 7 months, the median survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions: Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.

  18. Single dose oral analgesics for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

    2014-01-01

    Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130

  19. Inability of ibuprofen to alter single dose phenytoin disposition.

    PubMed Central

    Bachmann, K A; Schwartz, J I; Forney, R B; Jauregui, L; Sullivan, T J

    1986-01-01

    The effect of ibuprofen treatment (1600 mg day-1 per os for 7 days) on single dose (300 mg per os) dispositional parameters of phenytoin (DPH) was evaluated in 10 healthy males. Ibuprofen slightly increased the free fraction of DPH from mean (+/- s.d.) value of 6.9 (+/- 0.7)% to 7.8 (+/- 0.3)% (P less than 0.01). DPH total clearance (CL/F) was not significantly changed going from a value of 0.027 (+/- 0.009) 1 h-1 kg-1 to 0.032 (+/- 0.014) 1 h-1 kg-1 (0.05 less than P less than 0.1). Intrinsic unbound DPH clearance (CLuint/F) was unaffected by ibuprofen treatment. Neither DPH's apparent volume of distribution (V/F) nor the apparent volume of distribution of unbound DPH (Vunb/F) were significantly altered by ibuprofen treatment. The slight changes in DPH plasma protein binding that are due to concurrent ibuprofen treatment in doses of 1600 mg day-1 are not likely to produce important changes in DPH dispositional parameters. PMID:3954932

  20. The anthelmintic efficacy of albendazole against gastrointestinal roundworms, tapeworms, lungworms and liverflukes in sheep.

    PubMed

    van Schalkwyk, P C; Geyser, T L; Récio, M; Erasmus, F P

    1979-03-01

    Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica. PMID:551183

  1. EFficacy of albendazole for treatment of naturally acquired fasciola hepatica in calves.

    PubMed

    Malone, J B; Smith, P H; Loyacano, A F; Hembry, F G; Brock, L T

    1982-05-01

    In calves given various doses of albendazole as a 4.55% (w/v) drench suspension, removal efficacies against mature Fasciola hepatica were 77.5% with the dose of 7.5 mg/kg; 92.3%, with 10 mg/kg; and 85.9%, with 15 mg/kg. Against immature F hepatica, drug efficacies with these doses were 32.7%, 20.0%, and 36.7%, respectively. Reductions in length and width measurements of mature and immature flukes recovered from the bile ducts correlated with the larger doses reflected a greater efficacy against mature flukes or a possible inhibiting effect of the drug on fluke size or growth. Numbers of eggs recovered in bile at necropsy were reduced by 87.8% with the dose of 7.5 mg/kg; 91.8%, with 10 mg/kg; and 95.6%, with 15 mg/kg. PMID:7091853

  2. Single-Dose Pharmacokinetics and Safety of Ziprasidone in Children and Adolescents

    ERIC Educational Resources Information Center

    Sallee, Floyd R.; Miceli, Jeffrey J.; Tensfeldt, Thomas; Robarge, Lisa; Wilner, Keith; Patel, Nick C.

    2006-01-01

    Objective: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data. Method: A single-dose, open-label study of ziprasidone was conducted in youths…

  3. The effectiveness of 4 monthly albendazole treatment in the reduction of soil-transmitted helminth infections in women of reproductive age in Viet Nam.

    PubMed

    Mihrshahi, Seema; Casey, Gerard J; Montresor, Antonio; Phuc, Tran Q; Thach, Dang Thi Cam; Tien, Nong T; Biggs, Beverley-Ann

    2009-07-15

    Soil-transmitted helminth (STH) infections are endemic in northern Viet Nam where the climate and agricultural practices, such as the use of human excreta as fertiliser and the use of wastewater for irrigation, favour transmission. An intervention was conducted in Yen Bai Province, north-west Viet Nam, to measure the effectiveness of single dose albendazole (400mg) administered every 4 months for reducing the prevalence of STH infections in women of reproductive age. Stool samples were collected from women before the intervention and 3 and 12 months post-intervention. Information on a range of demographic and socio-economic variables was also collected to measure the major risk factors for high STH burden in this area. The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura infection in the baseline sample of 366 women were 76.2%, 19.2% and 29.1%, respectively. In the women who were surveyed at baseline and again at 3 and 12 months after the intervention (n=118) cure rates were 71.3% for hookworm, 87.0% for A. lumbricoides and 81.4% for T. trichiura by the end of the 12 month study period (i.e. after three doses of albendazole). The main risk factor for hookworm infection was if women worked outside (odds ratio (OR)=3.2 (95% Confidence Interval (CI) 1.6-6.2), P=0.001) and the major risk factor for A. lumbricoides and T. trichiura infection was a lack of education. Low educational attainment was also the strongest risk factor for co-infection with all three species of STH (OR=7.5 (95% CI 3.4-16.4), P<0.001). The high rates of hookworm infection in this area of Viet Nam and the high cure rates for all three species of STH with 4 monthly albendazole treatment suggest that this programme should be expanded to all endemic areas in Viet Nam. The study also highlights the important contribution of education to women's health. PMID:19324046

  4. 21 CFR 520.38a - Albendazole suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) body weight (10 mg/kilogram (kg)) as a single oral dose using dosing gun or dosing syringe. (ii... worms (thread-necked intestinal worm (Nematodirus spathiger and N. helvetianus), small intestinal worm....45 or 11.36 percent suspension: (i) Amount. 3.4 mg/lb body weight (7.5 mg/kg) as a single oral...

  5. Application of ultra-performance columns in high-performance liquid chromatography for determination of albendazole and its metabolites in turkeys.

    PubMed

    Grabowski, Tomasz; Jaroszewski, Jerzy Jan; Swierczewska, Anna; Sawicka, Renata; Maślanka, Tomasz; Markiewicz, Włodzimierz; Ziółkowski, Hubert

    2011-10-01

    Methods for determination of albendazole (ALB), albendazole sulfoxide (SOX) and albendazole sulfone (SON) in turkey blood plasma, using high-performance liquid chromatography (HPLC) with fluorescence detection, were developed. Moreover, comparison of HPLC columns with ultra-performance liquid chromatography (UPLC) columns was performed. Albendazol was administered orally in 5-week-old birds (n = 18) at a dose of 25 mg/kg b.w. Accuracy and precision of the developed method were satisfactory and stability studies showed acceptable variation (below 15%) in ALB, SOX and SON concentrations when the samples were stored at -75°C for 15 days. UPLC(®) columns gave higher peaks from typical HPLC columns retaining high quality of analysis. Pharmacokinetic analysis indicated quick elimination of ALB from turkey blood plasma. The mean residence time of SON was at least two times longer than that of SOX and four times longer than that of ALB. The elimination half-lives for ALB, SOX and SON were 0.7 ± 0.27, 5.37 ± 6.03, 9.17 ± 5.12 h, respectively. The obtained results indicate that the described method allows for precise determination of albendazole and its metabolites in turkey plasma. Moreover, using UPLC columns in HPLC apparatus results in higher sensitivity as compared with the classical HPLC columns. PMID:21294142

  6. Serial Myocardial Imaging after a Single Dose of Thallium-201.

    PubMed

    Kamata, Takahiko; Kawasaki, Tatsuya; Kamitani, Tadaaki; Sugihara, Hiroki

    2014-01-01

    Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year-old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise), showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise). Cardiac biomarkers were negative in the clinical course. PMID:27408869

  7. Serial Myocardial Imaging after a Single Dose of Thallium-201

    PubMed Central

    Kamata, Takahiko; Kawasaki, Tatsuya; Kamitani, Tadaaki; Sugihara, Hiroki

    2014-01-01

    Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year-old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise), showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise). Cardiac biomarkers were negative in the clinical course.

  8. Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections

    PubMed Central

    Dey, Sudipta Kumar; Das, Amal Kanti; Sen, Sumit; Hazra, Avijit

    2015-01-01

    Objectives: Uncomplicated skin and skin structure infections (uSSSIs) are a common clinical problem. Majority are caused by staphylococci and streptococci. Different oral antibiotics are used for uSSSI, with comparable efficacy but varying treatment duration, cost, and adverse event profile. Azithromycin is used in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g dose of the drug would produce a response in uSSSI comparable to conventional dosing. Materials and Methods: We conducted a parallel group, open-label, randomized, controlled trial (CTRI/2015/07/005969) with subjects of either sex, ≥12 years of age, presenting with uSSSI to the dermatology outpatient department. One group (n = 146) received 2 g single supervised dose while the other (n = 146) received conventional dose of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8. Complete clinical cure implied complete healing of lesions, without residual signs or symptoms, within 7 days. Results: High cure rate was observed in both arms (97.97% and 98.63%, respectively) along with noticeable improvement in symptom profile from baseline but without statistically significant difference between groups. However, excellent adherence (defined as no tablets missed) was better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable between groups with the majority of adverse events encountered being gastrointestinal in nature and mild. Conclusions: Single 2 g azithromycin dose achieved the same result as conventional azithromycin dosing in uSSSI with comparable tolerability but with the advantage of assured adherence. This dose can, therefore, be recommended as an alternative and administration supervised if feasible. PMID:26288467

  9. Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

    PubMed Central

    Aasmundstad, T A; Xu, B Q; Johansson, I; Ripel, A; Bjørneboe, A; Christophersen, A S; Bodd, E; Mørland, J

    1995-01-01

    1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology

  10. Effects observed on gestational day 13 in rat embryos exposed to albendazole.

    PubMed

    Mantovani, A; Ricciardi, C; Stazi, A V; Macrì, C

    1995-01-01

    Albendazole (ABZ) was utilized as a model to investigate the pathogenesis of benzimidazole-induced abnormalities. Pregnant Sprague-Dawley rats were treated po with 0, 10, 20, and 30 mg/kg on gestational days (GD) 10 to 12. The embryos were examined on GD 13, as a window for observing the origin of alterations detected at term. Embryolethality and growth reduction showed dose-related increases at the three dose levels. At 10 mg/kg, an increased developmental delay of limb buds and a less than 5% incidence of embryos with abnormal head or shape were detected. At 20 and 30 mg/kg, > 20% of embryos showed morphologic alterations involving mainly shape abnormalities and the development of forelimb buds, branchial bars, eye, and telencephalon; closure of neuropores was unaffected. Dose-response relationships for morphologic alterations showed steeper slopes than for growth reduction and embryolethality. PMID:7579911

  11. [Pharmacokinetics and urinary metabolism of albendazole in man].

    PubMed

    Penicaut, B; Maugein, P; Maisonneuve, H; Rossignol, J F

    1983-11-01

    Albendazole, a new broad spectrum benzimidazole anthelmintic, has been administered in 10 male volunteers. Administration was randomized using 100 mg tablets, 200 mg tablets and a 2% suspension. Blood samples were obtained 0.5; 1; 1.5; 2; 2.5; 3; 3.5; 4; 5; 6; 8; 12; 24; 72 h after treatment. Albendazole sulfoxide, one of the mains albendazole blood metabolites, was assayed by HPLC and the blood half life was calculated as 8 1/2 h. The three different pharmaceutical formulations were considered bioequivalent. Urines were collected, and using T. L. C. Technics, main metabolites were identified and characterized. Hydrolysis of the carbamate function and oxidation of the sulfur atom, the alkyle chain and the aromatic ring were the main biotransformations observed. PMID:6370482

  12. Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro.

    PubMed Central

    Didier, E S

    1997-01-01

    Presently, the two most commonly used drugs for treating microsporidiosis in persons with AIDS are albendazole and fumagillin. Albendazole is effective for treating disseminated infections due to Encephalitozoon spp. but is variably effective against Enterocytozoon bieneusi infections. Fumagillin is highly effective when used topically to treat ocular infections with Encephalitozoon hellem or Encephalitozoon intestinalis but is too toxic for systemic use. In this study, the fumagillin analog TNP-470 was assayed for antimicrosporidial activity in vitro. The MICs of TNP-470 at which 50% of isolates were killed (MIC50s) were 0.35 +/- 0.21 and 0.38 +/- 0.11 ng/ml for E. intestinalis and Vittaforma corneae, respectively, and were similar to the MIC50s of fumagillin for these organisms, which were 0.515 +/- 0.002 and 0.81 +/- 0.014 ng/ml, respectively. The MIC50 of albendazole for E. intestinalis was 8.0 +/- 4.23 ng/ml, significantly less (P < 0.01) than its MIC50 for V. corneae, which was 55.0 +/- 7.07 ng/ml. TNP-470 inhibited replication of E. intestinalis in RK-13 cells if it was given at the same time as infection or if treatment was initiated 7 days later. In addition, treatment of the infected cultures with TNP-470 at a dose of 10 ng/ml for 2 weeks, followed by discontinuation of the drug treatment, resulted in no significant increase in E. intestinalis shedding during the following 3 weeks in culture. Because TNP-470 acts against both E. intestinalis and V. corneae, and because TNP-470 was found by others to be less toxic in vivo, TNP-470 may be a promising new drug for the treatment of microsporidiosis. PMID:9210681

  13. Radiation pneumonitis following large single dose irradiation: a re-evaluation based on absolute dose to lung

    SciTech Connect

    Van Dyk, J.; Keane, T.J.; Kan, S.; Rider, W.D.; Fryer, C.J.H.

    1981-04-01

    The acute radiation pneumonitis syndrome is a major complication for patients receiving total thoracic irradiation in a large single dose. Previous studies have evaluated the onset of radiation pneumonitis on the basis of radiation doses calculated assuming unit density tissues. In this report, the incidence of radiation pneumonitis is determined as a function of absolute dose to lung. A simple algorithm relating dose correction factor to anterior-posterior patient diameter has been derived using a CT-aided treatment planning system. This algorithm was used to determine, retrospectively, the dose to lung for a group of 303 patients who had been treated with large field irradiation techniques. Of this group, 150 patients had no previous lung disease and had virtually no additional lung irradiation prior or subsequent to their large field treatment. The actuarial incidence of radiation pneumonitis versus dose to lung was evaluated using a simplified probit analysis. The resultant best fit sigmoidal complication curve demonstrates the onset of radiation pneumonitis to occur at about 750 rad with the 5% actuarial incidence occurring at approximately 820 rad. The errors associated with the dose determination procedure as well as the actuarial incidence calculations are considered. The time of onset of radiation pneumonitis occurs between 1 to 7 months after irradiation for 90% of the patients who developed pneumonitis with the peak incidence occurring at 2 at 3 months. No correlation was found between time of onset and the dose to lung over a dose range of 650 to 1250 rad.

  14. (13)C and (15)N solid-state NMR studies on albendazole and cyclodextrin albendazole complexes.

    PubMed

    Ferreira, M João G; García, A; Leonardi, D; Salomon, Claudio J; Lamas, M Celina; Nunes, Teresa G

    2015-06-01

    (13)C and (15)N solid-state nuclear magnetic resonance (NMR) spectra were recorded from albendazole (ABZ) and from ABZ:β-cyclodextrin, ABZ:methyl-β-cyclodextrin, ABZ:hydroxypropyl-β-cyclodextrin and ABZ:citrate-β-cyclodextrin, which were prepared by the spray-drying technique. ABZ signals were typical of a crystalline solid for the pure drug and of an amorphous compound obtained from ABZ:cyclodextrin samples. Relevant spectral differences were correlated with chemical interaction between ABZ and cyclodextrins. The number and type of complexes revealed a strong dependence on the cyclodextrin group substituent. Solid-state NMR data were consistent with the presence of stable inclusion complexes. PMID:25843843

  15. Dose fractionation and single subject studies in PET

    NASA Astrophysics Data System (ADS)

    Balakrishnan, Karthikayan

    Conventional positron emission tomography (PET) for cognitive brain studies typically relies on information collected from the distribution of decays following an injection of 15O-labeled water. The number of injections that can be administered to the subject are constrained by radiation dose to the subject and total length of the PET scan. The standard protocol involves 8--10 injections of H152O separated by approximately 5--7 half-lives of 15O. The number of activation conditions that can be realistically studied in a standard PET session is between 8 and 10. This work investigates the physiological response of a simulated subject to H152O injections that are administered in small doses (1--5 mCi) with short inter-injection intervals (40--180 seconds). A larger number of activation conditions are presented to the subject with a wider variation in the activation paradigm. Repeat conditions are studies. Signal averaging methods are feasible with this method of dose administration. Sinograms from scans with similar activation conditions are summed together before reconstruction. The signal in the primary activation region of the brain is shown to increase while suppressing the contribution of secondary activation regions in the brain. The contrast of the final image is similarly increased which leads to easier identification of the primary activation region. An automated H152O -production unit controlled by a PC running LabView software was developed to produce the dose required for the injection sequence by controlling the flow of H152O -vapor that diffuses across a semi-permeable membrane into saline. The unit is capable of producing H152O rapidly for both the standard and the proposed dose administration methods. The system also detects the bolus arrival time at the subject's lungs using a small external plastic detector. Activation sequence commences with the rise in radioactivity observed by the detector. The simulations indicate that inter-injection intervals

  16. Split-Dose Polyethylene Glycol Is Superior to Single Dose for Colonoscopy Preparation: Results of a Randomized Controlled Trial

    PubMed Central

    Mohamed, Rachid; Hilsden, Robert J.; Dube, Catherine; Rostom, Alaa

    2016-01-01

    Background. The efficacy of colonoscopy in detecting abnormalities within the colon is highly dependent on the adequacy of the bowel preparation. The objective of this study was to compare the efficacy, safety, and tolerability of PEG lavage and split-dose PEG lavage with specific emphasis on the cleanliness of the right colon. Methods. The study was a prospective, randomized, two-arm, controlled trial of 237 patients. Patients between the age of 50 and 75 years were referred to an outpatient university screening clinic for colonoscopy. Patients were allocated to receive either a single 4 L PEG lavage or a split-dose PEG lavage. Results. Overall, the bowel preparation was superior in the split-dose group compared with the single-dose group (mean Ottawa score 3.50 ± 2.89 versus 5.96 ± 3.53; P < 0.05) and resulted in less overall fluid in the colon. This effect was observed across all segments of the colon assessed. Conclusions. The current study supports use of a split-dose PEG lavage over a single large volume lavage for superior bowel cleanliness, which may improve polyp detection. This trial is registered with ClinicalTrials.gov identifier NCT01610856. PMID:27446836

  17. Single- and multiple-dose pharmacokinetics and dose proportionality of the psychotropic agent paliperidone extended release.

    PubMed

    Boom, Sandra; Talluri, Krishna; Janssens, Luc; Remmerie, Bart; De Meulder, Marc; Rossenu, Stefaan; van Osselaer, Nancy; Eerdekens, Marielle; Cleton, Adriaan

    2009-11-01

    Paliperidone extended-release tablet (paliperidone ER) is a centrally active dopamine D(2)- and serotonergic 5-HT(2A)-receptor antagonist that is registered for the treatment of schizophrenia. The controlled rate of release of paliperidone from the ER formulation is designed to have a slower absorption rate, which results in gradual ascending plasma concentrations with observed maximum plasma concentrations occurring at 24 hours after dosing on the first dosing day. On subsequent treatment days, the ER formulation provides minimal fluctuations in plasma concentrations. Paliperidone is eliminated with a terminal half-life of approximately 24 hours. Steady state is achieved after 4 daily doses. Paliperidone ER exhibits time-invariant pharmacokinetics. It shows a 3.5-fold accumulation upon steady state, mainly caused by the controlled release characteristics of the formulation. Paliperidone ER displays dose proportionality over the dose range of 3 to 15 mg; the 90% confidence intervals of the pairwise dose comparisons are all included in the 80% to 125% bioequivalence limits. PMID:19713555

  18. Albendazole sulphoxide kinetic disposition after treatment with different formulations in dogs.

    PubMed

    Dib, A; Palma, S; Suárez, G; Farías, C; Cabrera, P; Castro, S; Allemandi, D; Moreno, L; Lanusse, C; Sánchez Bruni, S

    2011-04-01

    New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO(2) were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration-time curve (+500%) and C(max) (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs. PMID:21395604

  19. In vitro Effects of Albendazole on Raillietina echinobothrida, the Cestode of Chicken, Gallus domesticus

    PubMed Central

    Lalchhandama, K

    2010-01-01

    Albendazole, a member of benzimidazole group of compounds, has been shown to have a broad spectrum activity against all classes of helminth parasites. Although it has also been experimentally proven to be effective against cestode infection of poultry, the actual effects of the drug are not yet described. The present in vitro study demonstrated that the commercial prescription drug Zentel® was significantly effective against adult Raillietina echinobothrida Mégnin, the major cestode parasite of domestic chicken, Gallus domesticus Linnaeus. It clearly exhibited dose-dependent lethal activity at the different concentrations that were tested. Scanning electron microscopy (SEM) revealed that the drug caused extensive structural alterations on the body surface of the cestode. Severe contraction and shrinkage were evident throughout the entire length of the body. The suckers on the scolex became invaginated due to shrinkage. The distinct body segments, the proglottides, were completely distorted. The fine hairy microtriches on the tegument were obliterated and in its place were formed abnormal clumps of tissues. The results of this investigation are in favor of the use of albendazole as a drug of choice in the management of poultry helminthiasis. PMID:21264097

  20. A comparative clinical trial of albendazole versus metronidazole in giardiasis.

    PubMed

    Misra, P K; Kumar, A; Agarwal, V; Jagota, S C

    1995-03-01

    The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents. In an open, randomized parallel group study, the safety and efficacy of albendazole was compared with that of metronidazole for the treatment of giardiasis in children. Sixty two children aged between 2-12 years were randomized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/kg thrice daily for 5 days. The mean days required for cure, as evident by absence of cysts and/or trophozoites in the stool specimen, was 3.7 + 1.4 and 4.5 + 1.1 days, respectively for children on albendazole and metronidazole therapy. Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment. Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of absence of anorexia. PMID:8613282

  1. Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine.

    PubMed

    Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R; Wu, T-C; Pai, Sara I

    2013-01-01

    Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8(+) T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8(+) T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8(+) T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic antitumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8(+) T cells, which led to higher ratios of CD8(+)/Treg and CD8(+)/CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8(+) T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

  2. Prevalence of soil-transmitted helminths after mass albendazole administration in an indigenous community of the Manu jungle in Peru

    PubMed Central

    Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A

    2014-01-01

    Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5–19 years (51.8 %) and 20–35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5–19 years [odd ratio (OR)  =  5.68; 95% CI: 2.71–11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon. PMID:24934795

  3. The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses.

    PubMed

    Posner, J; Bye, A; Dean, K; Peck, A W; Whiteman, P D

    1985-01-01

    The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions. PMID:3932079

  4. Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

    SciTech Connect

    Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M. )

    1993-03-20

    The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing [sup 60]Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs.

  5. Antiulcer prostaglandin misoprostol: single and multiple dose pharmacokinetic profile.

    PubMed

    Karim, A

    1987-01-01

    Low misoprostol dose (microgram range), extremely low plasma levels (pg range) of misoprostol acid, and the necessity of using a complex, time consuming, and labor intensive RIA method of analysis make it technically difficult to study the pharmacokinetic profile of misoprostol in man. The clinical relevance of the misoprostol pharmacokinetic data should be interpreted with care in view of the combined local and systemic effects of the drug. The studies presented in the present review indicate: Extensive metabolism of misoprostol occurs during and/or prior to gastrointestinal absorption. Several metabolites are formed and no unchanged drug is detected in the plasma or urine. The biologically active metabolite in the plasma is misoprostol acid (SC-30695), a de-esterified derivative of misoprostol. Absorption of misoprostol and/or misoprostol acid is extremely rapid resulting in peak plasma levels of misoprostol acid in less than 15 minutes. Absorption probably occurs in the stomach. The elimination half-life of misoprostol acid is short (less than 30 minutes). No accumulation of misoprostol acid occurs in plasma following a 400 microgram q12h dosing regimen of misoprostol. PMID:3122274

  6. Elimination kinetics of disulfiram in alcoholics after single and repeated doses.

    PubMed

    Faiman, M D; Jensen, J C; Lacoursiere, R B

    1984-10-01

    Elimination kinetics of disulfiram were determined in 15 male alcoholics after 250 mg disulfiram taken by mouth as a single dose and again after 12 days of dosing. Apparent t 1/2s were calculated for disulfiram, diethyldithiocarbamate (DDTC), diethyldithiocarbamate-methyl ester (DDTC-Me), diethylamine (DEA), and carbon disulfide (CS2) and were found to be 7.3, 15.5, 22.1, 13.9, and 8.9 hr. Elimination t 1/2 for CS2 in breath was 13.3 hr. Average time to reach maximal plasma concentration after either single or repeated doses was 8 to 10 hr for disulfiram, DDTC, DDTC-Me, DEA, and CS2 in breath, while plasma CS2 concentration peaked 5 to 6 hr after disulfiram. In these studies, 22.4% and 31.3% of the disulfiram after single and repeated dosing was eliminated in the breath during one dosing interval. In urine, 1.7% and 8.3% of the disulfiram dose was eliminated as DDTC-glucuronide after single and repeated dosing, while DEA accounted for 1.6% and 5.7% of the dose. There was marked intersubject variability in plasma levels of disulfiram and its metabolites. This variability may be the result of the lipid solubility of disulfiram, differences in plasma protein binding, or the effect of enterohepatic cycling. PMID:6090051

  7. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

    PubMed

    Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

    2015-04-01

    Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed. PMID:25691367

  8. Single or 2-Dose Micafungin Regimen for Treatment of Invasive Candidiasis: Therapia Sterilisans Magna!

    PubMed

    Gumbo, Tawanda

    2015-12-01

    The time the earth takes to rotate its axis (the day) has dictated how often pharmaceutical compounds are dosed. The scientific link between the 2 events is materia medica arcana. As an example, in the treatment of invasive candidiasis, antifungal therapy with intravenous micafungin is dosed daily. A literature review revealed population pharmacokinetic analyses, in vivo pharmacokinetics/pharmacodynamics studies, and maximum-tolerated-dose studies of micafungin that examined optimal micafungin dosing strategies. The half-life of micafungin in patient blood was 14 hours in several studies, but was even longer in different organs, so that the concentration will persist above minimum inhibitory concentrations of Candida species for several days. Studies in mice and rabbits with persistent neutropenia and disseminated candidiasis, otherwise fatal, demonstrated that a single large dose of micafungin could clear disseminated candidiasis, even though the micafungin half-life in such animals is shorter than in humans. Human pharmacokinetics/pharmacodynamics studies confirmed this link between micafungin efficacy and the ratio of the area under the concentration-time curve, and the optimal exposures initially identified in neutropenic animals. Maximum tolerated dose studies have demonstrated safety of 900 mg administered daily for several weeks, whereas case reports demonstrate efficacy and safety of single 1400-mg doses. Thus, a single dose of micafungin, or 2 such doses within a few days of each other, is not only logical, but might even lead to faster clearance of Candida. PMID:26567282

  9. Therapeutic efficacy of different brands of albendazole against soil transmitted helminths among students of Mendera Elementary School, Jimma, Southwest Ethiopia

    PubMed Central

    Tefera, Ephrem; Belay, Tariku; Mekonnen, Seleshi Kebede; Zeynudin, Ahmed; Belachew, Tefera

    2015-01-01

    Introduction Different brands Albendazole are commercially available and the efficacious brand/s is/are required for effective control of STHs infection. Thus, this study is aimed at determining the therapeutic efficacy of different brands of albendazole against soil transmitted helminths among school children of Jimma town. Methods A cross sectional survey for prevalence of geohelminths and a randomized trial for efficacy study of different brands of albendazole was conducted among students Mendera Elementary School from March 29 to April 29, 2010. Positive subjects were randomized into three treatment arms using lottery method. The collected stool samples were examined by the McMaster method. CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula. Results Of the 715 school children who had their stools examined, 326 were positive for STHs with a prevalence rate of 45.6%. The cure rates (CR) for A. lumbricoides, T. trichiura and Hookworm were 99.4, 59.9 and 93.7%, respectively. Similarly, the egg reduction rates (ERR) were 97, 99.9 and 99.9% respectively. A statistical significant mean STH egg count difference were observed between pre and post-intervention study (p <0.001). But no statistical significant curing effect difference were observed among the three brands used against the three STHs (p >0.05). Conclusion All the three brands of Albendazole tested regardless of the brand type were therapeutically efficacious for Ascariasis, Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple. PMID:26958115

  10. Single- and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT-116 (a TRPV1 antagonist) in dogs.

    PubMed

    Niyom, S; Mama, K R; Gustafson, D L; Rezende, M L

    2015-08-01

    Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5 μg·h/mL, T(max) of 3.7 h, and C(max) of 3.8 μg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 μg/mL previously determined for rodents) for analgesia during the 24-h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery in dogs. PMID:25376244

  11. Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

    PubMed Central

    Vercruysse, Jozef; Behnke, Jerzy M.; Albonico, Marco; Ame, Shaali Makame; Angebault, Cécile; Bethony, Jeffrey M.; Engels, Dirk; Guillard, Bertrand; Hoa, Nguyen Thi Viet; Kang, Gagandeep; Kattula, Deepthi; Kotze, Andrew C.; McCarthy, James S.; Mekonnen, Zeleke; Montresor, Antonio; Periago, Maria Victoria; Sumo, Laurentine; Tchuem Tchuenté, Louis-Albert; Thach, Dang Thi Cam; Zeynudin, Ahmed; Levecke, Bruno

    2011-01-01

    Background The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. Methodology/Principal Findings Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. Conclusions/Significance Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this

  12. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    PubMed Central

    Kim, Yo Han; Choi, Hee Youn; Noh, Yook-Hwan; Lee, Shi Hyang; Lim, Hyeong-Seok; Kim, Chin; Bae, Kyun-Seop

    2015-01-01

    Background Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR) formulation in healthy male subjects. Methods An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once). The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC) from time 0 to the last measurable time (AUClast), AUC extrapolated to infinity (AUCinf), and the measured peak plasma concentration (Cmax) were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs) of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs) throughout the study. Results A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359) for AUClast, 1.0003 (90% CI: 0.9748–1.0258) for AUCinf, and 0.9901 (90% CI: 0.9524–1.0277) for Cmax, respectively. All AEs were mild, and none of the subjects dropped out due to AEs. Conclusion In this study, exposure to carvedilol was proportional over the therapeutic dose range of 8–128 mg. The carvedilol SR formulation was well tolerated. PMID:26089641

  13. Immune Responses to Single-Dose Versus Double-Dose Hepatitis B Vaccines in Healthcare Workers not Responding to the Primary Vaccine Series: A Randomized Clinical Trial

    PubMed Central

    Joukar, Farahnaz; Mansour-Ghanaei, Fariborz; Naghipour, Mohammad-Reza; Asgharnezhad, Mehrnaz

    2016-01-01

    Background Recommendations to immunize healthcare workers (HCWs) against hepatitis B are well known. However, a proportion of individuals do not respond to the primary standard three-dose HB vaccination schedule. Objectives The current study aimed to evaluate whether a double-dose HB booster vaccine could induce better protective anti-HB titers than a single-dose booster in non-protected HCWs. Materials and Methods This was a randomized clinical trial. A total of 91 HCWs not responding to the primary vaccine series in 2014 were enrolled. The participants were randomized into two groups that received a double dose of the HB vaccine containing 40 µg of antigen or a single dose of the HB vaccine containing 20 µg of antigen in three doses (at zero, one and six months after vaccination). Blood samples were collected before vaccinations and 28 days after the third dose to assess the seroconversion rate, according to the anti-HB antibody titer threshold of > 10 mIU/mL. Results The seroconversion rates were 93.2% and 87.2% after the first booster doses of the double-dose and single-dose HB vaccines, respectively (P = 0.64). In the double-dose HB vaccine group, the seroconversion rate was 97.8% compared with 89.6% in the single-dose group following the second vaccine dose (P = 0.83). All of the participants in both groups were seroprotected after the third HB vaccine dose. Conclusions Both the single- and double-dose HB vaccines were adequately immunogenic, and the double-dose HB vaccine was not significantly more immunogenic than the single-dose vaccine in terms of the seroconversion rates of HCWs who had not responded to the primary vaccine series. PMID:27148385

  14. Therapy of human hydatid disease with mebendazole and albendazole.

    PubMed Central

    Teggi, A; Lastilla, M G; De Rosa, F

    1993-01-01

    We report our experience in the treatment with benzoimidazole carbamates (mebendazole and albendazole) of 337 patients affected by hydatid cysts with different localizations. The treated cysts showed degenerative modifications in 50.6% of the cases after mebendazole treatment and in about 80% after albendazole treatment. Relapses after therapy were observed in 30% of the cases; about 95% of the recurring cysts showed good susceptibility to a further cycle of therapy with benzoimidazole carbamates. Side effects observed with either drug were not severe and always reversible, consisting mainly of abdominal pains and increased levels of transaminases in serum. Among the factors that may influence the therapeutic results are the drug employed, the age of the cysts, the age of the patient, and the localization of the cysts and their morphological characteristics. Moreover, it can be hypothesized that each hydatid cyst has an intrinsic sensitivity to benzoimidazole carbamates. PMID:8215283

  15. Search for one-dose tetanus vaccine approaches first deadline. CVI goal: lifelong protection with a single-dose vaccine.

    PubMed

    1995-10-01

    Progress is reported among a Children's Vaccine Initiative (CVI) product development working group on the development of a single-dose tetanus toxoid vaccine that would change the current three-dose schedule of the diphtheria-tetanus-pertussis (DTP) combination vaccine. Development involved the participation of the vaccine development component of the World Health Organization's Global Program for Vaccines and Immunization. The single-dose approach is one in which the tetanus toxoid antigen is embedded in tiny synthetic microcapsules or microspheres, which are a mix of polymers (mostly lactic and glycolic acids). The size of the capsules and their composition determine the rate and schedule of release of the toxoid. Administration is usually by injection, but oral administration is being examined. The aim is for coverage within weeks of administration and provision of boosters one or two months later and again after eight to twelve months. Testing showed that responses were initially strong, but were inadequate one month or more later. Experimentation is ongoing using chemical modifications of the toxoid, changes in stabilizing agents, and higher concentrations of toxoids. An Australian company is ready for animal testing of its single-dose version. A Phase I safety trial is planned for an oral recombinant vaccine comprising a Salmonella vector transfected with the gene for the tetanus toxoid C fragment. Animal tests, so far inconclusive, have been conducted with a vaccine in which the alum adjuvant is replaced with a more powerful adjuvant. The working group has a number of vaccine research development projects that are at the initial stages. PMID:12290721

  16. Uptake of albendazole and albendazole sulphoxide by Haemonchus contortus and Fasciola hepatica in sheep.

    PubMed

    Alvarez, L I; Imperiale, F A; Sánchez, S F; Murno, G A; Lanusse, C E

    2000-12-20

    The pattern of in vivo uptake of albendazole (ABZ) and its major metabolite, ABZ-sulphoxide (ABZSO), by Haemonchus contortus and Fasciola hepatica recovered from ABZ-treated sheep, was investigated. Concentration profiles of both compounds were simultaneously measured in target tissues/fluids from the same infected sheep. In addition, the proportion of the (+) and (-) ABZSO enantiomers was determined in plasma, bile and F. hepatica recovered from treated sheep. Sheep naturally infected with H. contortus were intraruminally (i.r.) treated with ABZ (micronized suspension, 7. 5mg/kg) and the plasma concentrations of ABZSO and ABZ-sulphone (ABZSO(2)) determined in addition to the concentration of ABZ and ABZSO in H. contortus, abomasal mucosa and fluid content samples. In addition, F. hepatica artificially infected sheep were treated i.r. with the same ABZ suspension (7.5mg/kg), and samples of blood, bile, liver tissue and adult flukes were collected and analysed by HPLC to determine the concentrations of ABZ and both enantiomers of ABZSO. ABZSO and ABZSO(2) were the analytes recovered in plasma with ABZ and ABZSO present in H. contortus. ABZ was the analyte recovered at the highest concentration in H. contortus and abomasal mucosa, whereas higher concentrations of ABZSO were measured in abomasal fluid content. Only low concentrations of ABZ were detected in F. hepatica and bile, but markedly higher concentrations of ABZ were measured in liver tissue. ABZSO was the main molecule recovered in F. hepatica, plasma and bile samples collected from ABZ-treated sheep. The (+) enantiomer of ABZSO was recovered at a higher proportion in plasma (75%), bile (78%) and F. hepatica (74%) after ABZ administration to infected sheep. PMID:11078946

  17. Cellular response of the rat brain to single doses of 137Cs γ rays does not predict its response to prolonged ‘biologically equivalent’ fractionated doses

    PubMed Central

    Greene-Schloesser, Dana M.; Kooshki, Mitra; Payne, Valerie; D’Agostino, Ralph B.; Wheeler, Kenneth T.; Metheny-Barlow, Linda J.; Robbins, Mike E.

    2014-01-01

    Purpose To determine if the brain’s response to single doses predicts its response to ‘biologically equivalent’ fractionated doses. Methods Young adult male Fischer 344 rats were whole-brain irradiated with either single 11, 14, or 16.5 Gy doses of 137Cs γ rays or their ‘biologically equivalent’ 20, 30, or 40 Gy fractionated doses (fWBI) delivered in 5 Gy fractions, twice/week for 2, 3, or 4 weeks, respectively. At 2 months post-irradiation, cellular markers of inflammation (total, activated, and newborn microglia) and neurogenesis (newborn neurons) were measured in 40 µm sections of the dentate gyrus (DG). Results Although the total number of microglia in the DG/hilus was not significantly different (p > 0.7) in unirradiated, single dose, and fWBI rats, single doses produced a significant (p < 0.003) increase in the percent-activated microglia; fWBI did not (p > 0.1). Additionally, single doses produced a significant (p < 0.002) dose-dependent increase in surviving newborn microglia; fWBI did not (p < 0.8). Although total proliferation in the DG was reduced equally by single and fWBI doses, single doses produced a significant dose-dependent (p < 0.02) decrease in surviving newborn neurons; fWBI did not (p > 0.6). Conclusions These data demonstrate that the rat brain’s cellular response to single doses often does not predict its cellular response to ‘biologically equivalent’ fWBI doses. PMID:24937374

  18. Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.

    PubMed Central

    Chen, Z R; Bochner, F; Somogyi, A

    1988-01-01

    1. The pharmacokinetics of pholcodine after two single doses and after chronic administration were studied in healthy human volunteers. 2. Six subjects received single oral doses of 20 and 60 mg of pholcodine according to a balanced cross-over design with an interval of 3 weeks between the two treatments. Blood and saliva samples and all urine were collected over 168 h after each dosage administration. Subsequently, the same subjects received 20 mg pholcodine 8 hourly orally for 10 days. Blood and saliva samples and all urine were collected during an 8 h dosing interval after the last dose on day 11. 3. Plasma, saliva and urine concentrations of pholcodine were determined by a high performance liquid chromatographic assay. 4. After the single doses, pholcodine was absorbed rapidly (tmax = 1.6 +/- 1.2 h) and eliminated slowly with a mean half-life of 50.1 +/- 4.1 h. The renal clearance of pholcodine was 137 +/- 34 ml min-1 and was inversely correlated with urine pH (r = 0.60) but not with urine flow rate. 26.2 +/- 3.3% of the dose was excreted as unchanged pholcodine after both doses. The concentration of pholcodine in saliva was 3.6 times higher than in plasma. 5. After chronic administration, the pharmacokinetics of pholcodine were not statistically different from the single dose parameters. 6. Pholcodine did not appear to undergo conjugation. The plasma protein binding was 23.5%. Morphine, in unconjugated or conjugated form, was not detected in the urine of any subject after pholcodine administration. PMID:3190994

  19. Bone marrow aplasia and severe skin rash after a single low dose of methotrexate.

    PubMed

    Copur, S; Dahut, W; Chu, E; Allegra, C J

    1995-02-01

    A 64 year old man with recurrent metastatic squamous cell carcinoma of the head and neck developed severe skin rash and bone marrow aplasia 4 and 7 days, respectively, following a single dose of 40 mg/m2 methotrexate (MTX). Skin rash involved regions of the face, lower abdomen, back, buttocks and both upper thighs. Biopsy of the skin rash demonstrated superficial perivascular lymphocytic infiltrate and was consistent with a drug reaction. Peripheral blood count revealed pancytopenia and a bone marrow biopsy was consistent with aplasia. Blood counts returned to normal 6 days after institution of granulocyte colony stimulating factor therapy. In the absence of mucositis or diarrhea, severe dermatologic toxicity following a single low dose of the drug suggests an 'allergic' or acute hypersensitivity reaction to MTX in this patient. Development of an extensive skin rash following a single dose of MTX may be an early warning sign for life-threatening bone marrow aplasia. PMID:7538828

  20. Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

    NASA Astrophysics Data System (ADS)

    Tang, Grace; Earl, Matthew A.; Yu, Cedric X.

    2009-11-01

    Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc™ deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to <=± 5°. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was delivered

  1. Mouse Single Oral Dose Toxicity Study of DHU001, a Polyherbal Formula

    PubMed Central

    Roh, Seong-Soo

    2010-01-01

    This study was conducted to obtain acute information of the oral dose toxicity of DHU001, a polyherbal formula in male and female mice. In order to calculated 50% lethal dose (LD50) and approximate lethal dose (LD) , test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (vehicle control) ml/kg (body weight) . The mortality and changes on body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with DHU001. We could not find any mortalities, DHU001 treatment-related clinical signs, changes on the body and organ weights, gross and histopathological findings. The results obtained in this study suggest that LD50 and approximate LD in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both female and male mice. PMID:24278506

  2. Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats.

    PubMed

    Feuston, M H; Kerstetter, S L; Wilson, P D

    1990-10-01

    2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0, 250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly (p less than 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg. PMID:2258010

  3. Tumor induction in mice following localized single or fractionated dose irradiation: differences in tumor histotype and genetic susceptibility based on dose scheduling

    PubMed Central

    Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.

    2015-01-01

    Purpose To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single dose or clinically relevant, fractioned dose γ-ray radiation. Methods C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gray (Gy) or fractionated doses totaling 40 to 80 Gy delivered at 2 Gy/day fractions, 5 days/week, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days following irradiation and all tumors were characterized histologically. Results A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed following fractionated irradiation (16.4%) in comparison to single dose irradiation (36.1%). Sarcomas were the predominant post-irradiation tumor observed (n = 201) with carcinomas occurring less frequently (n = 9). The proportion of mice developing tumors increased significantly with total dose for both single dose and fractionated schedules and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice following single dose irradiation, however, significant differences in tumor susceptibilities following fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common following fractionated irradiation whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common following single dose irradiation. Conclusions This study investigated the tumorigenic effect of acute large doses in comparison to fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiotherapy. Differences in tumor histotype following single dose or fractionated radiation exposures provides novel in vivo evidence for differences in tumor

  4. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

    SciTech Connect

    Edmondson, Elijah F.; Hunter, Nancy R.; Weil, Michael M.; Mason, Kathryn A.

    2015-07-15

    Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor

  5. Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

    PubMed

    Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

    1988-01-01

    The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels. PMID:3365282

  6. Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis).

    PubMed

    Venturina, Virginia M; Alejandro, Ma Antonette F; Baltazar, Cyril P; Abes, Nancy S; Mingala, Claro N

    2015-01-01

    Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals. PMID:26878627

  7. The effect of intestinal trichinellosis on oral bioavailability of albendazole in mice.

    PubMed

    Rodríguez, Juan José García; de Prada, Inmaculada; Durán, Juan José Torrado; Fernández, Francisco Bolás

    2009-07-01

    The effect of Trichinella spiralis infection on the pharmacokinetic profile of orally administered albendazol has been investigated in mice during the intestinal phase of the disease. Swiss CD-1 mice were orally infected with 300 +/- 50 muscle larvae of T. spiralis and then treated with albendazole (ABZ) formulated in hydroxy-propyl-beta-cyclodextrins at the dose of 10 mg/kg given orally on days 0, 5, 10 and 22 post-infection (p.i.). Blood samples were taken at 0.25, 0.5, 0.75, 1, 5, 6 and 24 h post-treatment (p.t.). Adult worm establishment as well as the histopathological alterations induced in the small intestine was assessed on days 0, 5, 10 and 22 p.i. The area under the blood concentrations to time curve (AUC) for ABZ sulphoxide was not significantly higher in infected mice than in control during the first step of intestinal infection (day 5 p.i.), whereas in the late step (day 10 p.i.), it was significantly lower. On day 22 p.i., the AUC showed similar values in both groups. The histopathological analysis showed a transient acute inflammatory reaction that varied from moderate to severe as the infection progressed from the early to the late intestinal stage. After intestinal infection, the inflammation was mild or absent with no signs of chronic effects. The histopathological studies correlated with the pharmacokinetics of ABZ and show that after transient inflammation induced by intestinal T. spiralis infection, the mucosa is restored to allow absorption of ABZ up to levels comparable to those observed in non-infected controls. PMID:19241092

  8. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

    PubMed Central

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  9. Prolonged central mu-opioid receptor occupancy after single and repeated nalmefene dosing.

    PubMed

    Ingman, Kimmo; Hagelberg, Nora; Aalto, Sargo; Någren, Kjell; Juhakoski, Auni; Karhuvaara, Sakari; Kallio, Antero; Oikonen, Vesa; Hietala, Jarmo; Scheinin, Harry

    2005-12-01

    The opioid antagonist nalmefene offers an alternative to traditional pharmacological treatments for alcoholism. The present study was designed to investigate the relationship between nalmefene plasma concentration and central mu-opioid receptor occupancy after a clinically effective dose (20 mg, orally). Pharmacokinetics and mu-opioid receptor occupancy of nalmefene after single and repeated dosing over 7 days was studied in 12 healthy subjects. Serial blood samples were obtained after both dosings, and pharmacokinetic parameters for nalmefene and main metabolites were determined. Central mu-opioid receptor occupancy of nalmefene was measured with positron emission tomography (PET) and [(11)C]carfentanil at four time points (3, 26, 50, 74 h) after both dosings. Nalmefene was rapidly absorbed in all subjects. The mean t(1/2) of nalmefene was 13.4 h after single and repeated dosing. The accumulation of nalmefene and its main metabolites in plasma during the repeated dosing period was as expected for a drug with linear pharmacokinetics, and steady-state was reached for all analytes. Both nalmefene dosings resulted in a very high occupancy at mu-opioid receptors (87-100%), and the decline in the occupancy was similar after both dosings but clearly slower than the decline in the plasma concentration of nalmefene or metabolites. High nalmefene occupancy (83-100%) persisted at 26 h after the dosings. The prolonged mu-opioid receptor occupancy by nalmefene indicates slow dissociation of the drug from mu-opioid receptors. These results support the rational of administering nalmefene when needed before alcohol drinking, and they additionally suggest that a high mu-opioid receptor occupancy can be maintained when nalmefene is taken once daily. PMID:15956985

  10. Effect of multiple doses of omeprazole on the pharmacokinetics, pharmacodynamics, and safety of a single dose of rivaroxaban.

    PubMed

    Moore, Kenneth Todd; Plotnikov, Alexei Nikolaevich; Thyssen, An; Vaccaro, Nicole; Ariyawansa, Jay; Burton, Paul Bryan

    2011-12-01

    Many patients with acute coronary syndrome receive chronic dual antiplatelet therapy (acetylsalicylic acid and clopidogrel) for secondary event prophylaxis, and new oral anticoagulants are being investigated as adjunctive therapy in this indication. Gastrointestinal side effects such as bleeding are commonly associated with antiplatelet use; accordingly, many patients receive proton pump inhibitors (PPIs) to mitigate this. PPIs can reduce the antiplatelet activity of clopidogrel through cytochrome P450 2C19 inhibition, and pantoprazole reduces the bioavailability of dabigatran, a direct thrombin inhibitor that acts via cytochrome P450 2C19-independent mechanisms. These observations support the investigation of potential pharmacokinetic and pharmacodynamic interactions between PPIs and anticoagulants. We evaluated the influence of administering once-daily omeprazole 40 mg for 5 days on the pharmacokinetics and pharmacodynamics of a single 20-mg dose of the oral direct factor Xa inhibitor, rivaroxaban, in a randomized, open-label, 2-way, crossover, drug-drug interaction study in healthy subjects. No clinically meaningful interactions were observed; geometric mean ratios were 101%, 101%, and 93.5% for rivaroxaban area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast), or until infinity (AUC∞), and maximum plasma concentration (Cmax), respectively. Prothrombin time increased similarly in both treatment groups, with maximal values observed approximately 4 hours post rivaroxaban administration. A single 20-mg rivaroxaban dose appears well tolerated when administered alone or after 5 days of once-daily omeprazole 40 mg administration. PMID:21822144

  11. The use of albendazole for the treatment of trematodiasis in two tree shrews (Tupala glis)

    USGS Publications Warehouse

    Beehler, B.A.; Tuggle, B.N.

    1983-01-01

    Albendazole is a broad-spectrum anthelmintic of the benzimidazole group which has been tested in several rodents and domestic animals. Albendazole has been used effectively to treat trematodes in sheep, cattle, dogs, and cats. The use of this anthelmintic in exotic small mammals has not been reported to the authors' knowledge.

  12. Diet-induced modulation of pharmacokinetics of albendazole in Sahiwal cattle.

    PubMed

    Sanyal, P K; Rawte, D; Kerketta, A E; Kumbhakar, N K; Kumar, D; Pal, S; Baghel, K R; Bisen, S

    2016-09-01

    The influence of diet type and pre-treatment fasting on the kinetic disposition of albendazole was evaluated in Sahiwal heifers following oral and intra-ruminal administration of the drug. The anthelmintically active moiety albendazole sulphoxide appeared early and was eliminated early in cattle offered green fodder, with decreased maximum concentration (C max) and area under concentration-time curve (AUC) when the drug was administered both through oral and intra-ruminal routes. Further, the elimination half-life (t ½β) revealed significantly increased values for albendazole sulphoxide in cattle administered albendazole through the intra-ruminal route. An increased AUC and t ½β is reflective of increased bioavailability of albendazole in animals offered dry fodder. Increased values (P <  0.05) of C max, time to C max (T max), AUC and t ½β for albendazole sulphoxide occurred in cattle with a pre-treatment 24-h fast, resulting in its increased bioavailability. Extrapolation of data of the active metabolite albendazole sulphoxide levels in terms of drug-parasite contact revealed increased exposure of parasites to the drug in cattle administered albendazole through the intra-ruminal route and with 24-h pre-treatment fasting. PMID:26306773

  13. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    SciTech Connect

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A. )

    1990-12-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.

  14. Treatment of uncomplicated gonorrhea with single-dose imipenem-cilastatin.

    PubMed Central

    Verdon, M S; Judson, F N; Ehret, J M; Root, C J; Hook, E W; McCormack, W M; Frances, C A; Draft, K; Shands, J W; Handsfield, H H

    1988-01-01

    Single 500-mg intramuscular doses of imipenem-cilastatin cured 116 (95%) of 122 men and 9 of 9 women with uncomplicated gonorrhea due to beta-lactamase-negative Neisseria gonorrhoeae. Most co-existing Chlamydia trachomatis infections persisted. Imipenem-cilastatin is effective for uncomplicated gonorrhea in men but has no advantages over other available regimens. PMID:3395105

  15. Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder.

    PubMed

    Enter, Dorien; Terburg, David; Harrewijn, Anita; Spinhoven, Philip; Roelofs, Karin

    2016-01-01

    Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially dominant gaze behavior. Therefore we tested as a proof of principle whether single dose testosterone administration can reduce gaze avoidance in SAD. In a double-blind, within-subject design, 18 medication-free female participants with SAD and 19 female healthy control participants received a single dose of 0.5mg testosterone and a matched placebo, at two separate days. On each day, their spontaneous gaze behavior was recorded using eye-tracking, while they looked at angry, happy, and neutral facial expressions. Testosterone enhanced the percentage of first fixations to the eye-region in participants with SAD compared to healthy controls. In addition, SAD patients' initial gaze avoidance in the placebo condition was associated with more severe social anxiety symptoms and this relation was no longer present after testosterone administration. These findings indicate that single dose testosterone administration can alleviate gaze avoidance in SAD. They support theories on the dominance enhancing effects of testosterone and extend those by showing that effects are particularly strong in individuals featured by socially submissive behavior. The finding that this core characteristic of SAD can be directly influenced by single dose testosterone administration calls for future inquiry into the clinical utility of testosterone in the treatment of SAD. PMID:26402923

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  17. Dose Control System in the Optima XE Single Wafer High Energy Ion Implanter

    SciTech Connect

    Satoh, Shu; Yoon, Jongyoon; David, Jonathan

    2011-01-07

    Photoresist outgassing can significantly compromise accurate dosimetry of high energy implants. High energy implant even at a modest beam current produces high beam powers which create significantly worse outgassing than low and medium energy implants and the outgassing continues throughout the implant due to the low dose in typical high energy implant recipes. In the previous generation of high energy implanters, dose correction by monitoring of process chamber pressure during photoresist outgassing has been used. However, as applications diversify and requirements change, the need arises for a more versatile photoresist correction system to match the versatility of a single wafer high energy ion implanter. We have successfully developed a new dosimetry system for the Optima XE single wafer high energy ion implanter which does not require any form of compensation due to the implant conditions. This paper describes the principles and performance of this new dose system.

  18. Dose Control System in the Optima XE Single Wafer High Energy Ion Implanter

    NASA Astrophysics Data System (ADS)

    Satoh, Shu; Yoon, Jongyoon; David, Jonathan

    2011-01-01

    Photoresist outgassing can significantly compromise accurate dosimetry of high energy implants. High energy implant even at a modest beam current produces high beam powers which create significantly worse outgassing than low and medium energy implants and the outgassing continues throughout the implant due to the low dose in typical high energy implant recipes. In the previous generation of high energy implanters, dose correction by monitoring of process chamber pressure during photoresist outgassing has been used. However, as applications diversify and requirements change, the need arises for a more versatile photoresist correction system to match the versatility of a single wafer high energy ion implanter. We have successfully developed a new dosimetry system for the Optima XE single wafer high energy ion implanter which does not require any form of compensation due to the implant conditions. This paper describes the principles and performance of this new dose system.

  19. Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

    SciTech Connect

    Zhang, Hualin E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.; Cao, Minsong; Das, Indra J.

    2014-02-15

    Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was at the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional

  20. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

    PubMed Central

    Berry-Kravis, E; Hessl, D; Coffey, S; Hervey, C; Schneider, A; Yuhas, J; Hutchison, J; Snape, M; Tranfaglia, M; Nguyen, D V; Hagerman, R

    2009-01-01

    Objective: A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS). Methods: Twelve subjects, recruited from two fragile X clinics, received a single oral dose of 50–150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition. Results: There were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects. Conclusions: Clinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS. PMID:19126569

  1. Guaifenesin Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

    PubMed

    Thompson, Gary A; Solomon, Gail; Albrecht, Helmut H; Reitberg, Donald P; Guenin, Eric

    2016-07-01

    This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age-based doses of 100-400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo ) and terminal volume of distribution (Vz /F) increased with age. Due to a larger increase in Vz /F than CLo , an increase in terminal exponential half-life was also observed. Allometric scaling indicated no maturation-related changes in CLo and Vz /F. PMID:26632082

  2. Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

    PubMed Central

    2013-01-01

    Background Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. Patients and methods From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Results Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. Conclusion This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment

  3. Effects of total dose irradiation on single-event upset hardness.

    SciTech Connect

    Paillet, Philippe; Ferlet-Cavrois, V.; Flores, Richard S.; Schwank, James Ralph; Felix, James Andrew; Shaneyfelt, Marty Ray; Hash, Gerald Leon; Cole, Edward Isaac, Jr.; Blackmore, E. W.; Dodd, Paul Emerson; Baggio, J.

    2005-04-01

    The effect of total dose on SEU hardness is investigated as a function of temperature and power supply voltage to determine worst case hardness assurance test conditions for space environments. SRAMs from six different vendors were characterized for single-event upset (SEU) hardness at proton energies from 20 to 500 MeV and at temperatures of 25 and 80 C after total dose irradiating the SRAMs with either protons, Co-60 gamma rays, or low-energy x-rays. It is shown that total dose irradiation and the bias configuration during total dose irradiation and SEU characterization can substantially affect SEU hardness for some SRAMs. For one SRAM, the bias configuration made more than two orders of magnitude difference in SEU cross section at the highest total dose level examined. In addition, it is shown that increasing the temperature during SEU characterization can also increase the effect of total dose on SEU hardness. As a result, worst-case SEU hardness assurance test conditions are the maximum total dose and temperature of the system environment, and the minimum operating voltage of the SRAM. In contrast to previous works, our results using selective area x-ray irradiations show that the source of the effect of total dose on SEU hardness is radiation-induced leakage currents in the memory cells. The increase in SEU cross section with total dose appears to be consistent with radiation-induced currents originating in the memory cells affecting the output bias levels of bias level shift circuitry used to control the voltage levels to the memory cells and/or due to the lowering of the noise margin of individual memory cells caused by radiation-induced leakage currents.

  4. SINGLE- VERSUS DOUBLE-DOSE RABIES VACCINATION IN CAPTIVE AFRICAN WILD DOGS (LYCAON PICTUS).

    PubMed

    Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

    2015-12-01

    The immune responses of 35 captive African wild dogs (Lycaon pictus) to an inactivated rabies virus vaccine were evaluated. Seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. Sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. Rabies neutralizing serum antibody titers were measured by rapid fluorescent focus inhibition testing. Within 3 mo postvaccination, all 28 animals that were tested within that time period had seroconverted. Overall, titers were significantly higher among animals given two doses of vaccine than among those given a single dose, although this difference was no longer significant by 15 mo postvaccination. Regardless of initial dose, a single administration of inactivated rabies virus vaccine resulted in long-term elevation of titers in the African wild dogs in this study. In the two individuals followed for greater than 36 mo, both (one from each group) maintained detectable titers. PMID:26667524

  5. Pharmacokinetics and cyclooxygenase inhibition of itazigrel in normal volunteers after single oral doses.

    PubMed

    Hsyu, P H; Koets, M D; Luderer, J R

    1994-12-01

    The pharmacokinetics and cyclooxygenase inhibition of itazigrel were studied in normal male volunteers. In a low-dose study, subjects received a single oral dose of 5-100 mg of itazigrel. Serum concentration and the production rate of thromboxane B2, an indicator of cyclooxygenase activity, were monitored for 48 h. In a high-dose study, single oral doses of 100-600 mg of itazigrel were administered. Serum concentrations were monitored for 72 h. Production rates of thromboxane B2 and leukotriene B4, an indicator of lipoxygenase activity, were monitored for the first 2 h after drug administration. Pharmacokinetics of itazigrel appeared to follow biexponential elimination with an alpha half-life between 1.2 and 2 h and a beta half-life between 23 and 28 h. The relationship between dose and area under the serum concentration curve was nonlinear, probably due to saturable systemic metabolism or saturable first-pass metabolism. Cyclooxygenase inhibition by itazigrel was related to the serum concentration by the Hill's equation with a mean IC50 value of 2.1 ng/mL. Itazigrel did not appear to affect the lipoxygenase activity in the study. PMID:7891305

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

    PubMed

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

    2015-01-01

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

  7. 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

  8. Single doses of ivermectin 400 micrograms/kg-1: the most effective dosage in bancroftian filariasis.

    PubMed

    Moulia-Pelat, J P; Glaziou, P; Nguyen, L N; Cartel, J L

    1995-03-01

    Forty-three Wuchereria bancrofti carriers were given four successive semi-annual single doses of ivermectin 100 micrograms.kg-1 (IVER 100). The geometric mean microfilaremia (mf) recurrence percentage as compared to the pre-initial treatment mf level was 35%, 21%, 17% and 17% at 6, 12, 18 and 24 months, respectively. However, the recurrence of mf 6 months after the fourth treatment remained high in several individuals: 15 have been considered as 'bad responders' and 28 as 'good responders' individuals. At month 24 (M 24), they were randomly allocated into 2 groups. A first group was treated with a fifty and a sixth dose of IVER 100, at M24 and M30, respectively; the second one was treated, at the same time, with single doses of IVER 400 micrograms.kg-1 (IVER 400). At M 36, the mf recurrence percentage (mf M36/mf M0) was significantly higher in patients treated with IVER 100 than IVER 400 (11% vs 1%, p < 10(-4). From the group IVER 100, 6 out of the 8 'bad responders' remained 'bad responders' whereas there were none of the 7 in the group IVER 400. Moreover, there were only 2 more patients in the group IVER 100 showing sustained complete zero mf, whereas they were 13 in the group IVER 400. Single doses of IVER 400 were effective on 'bad responders'; IVER 400 must be recommended for semi-annual mass treatment in bancroftian filariasis. PMID:8525398

  9. Effects of single-dose and fractionated cranial irradiation on rat brain accumulation of methotrexate

    SciTech Connect

    Kamen, B.A.; Moulder, J.E.; Kun, L.E.; Ring, B.J.; Adams, S.M.; Fish, B.L.; Holcenberg, J.S.

    1984-11-01

    The effects of single-dose and fractionated whole-brain irradiation on brain methotrexate (MTX) has been studied in a rat model. The amount of MTX present in the brain 24 hr after a single i.p. dose (100 mg/kg) was the same whether animals were sham irradiated or given a single dose of 2000 rads 6 or 48 hr prior to the drug (6.9, 8.3, and 6.8 pmol MTX/g, wet weight, respectively). Animals sham irradiated or given 2000 rads in 10 fractions over 11 days and treated with an average dose of 1.2 mg MTX/kg i.p. twice a week for 24 weeks did not differ significantly in their brain MTX concentration (7.9 and 8.3 pmol MTX/g, wet weight, respectively). Chronically MTX-treated animals became folate deficient whether they were irradiated or not (450 and 670 pmol folate/g, wet weight, brain in MTX-treated and control animals). Thus, MTX accumulates in the brain with acute or chronic administration, and this accumulation is not altered by this amount of brain irradiation.

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

    PubMed Central

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

    2015-01-01

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

  11. Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers.

    PubMed

    Jacobs, Birgit S; Colbers, Angela P H; Velthoven-Graafland, Kirsten; Schouwenberg, Bas J J W; Burger, David M

    2014-08-01

    Psychosis and other mental illnesses are common in HIV-infected patients. Olanzapine is one of the preferred antipsychotic agents for the treatment of schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown. Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir. To compensate for the induction of olanzapine metabolism by fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15 mg with fosamprenavir/ritonavir would lead to a similar area under the concentration-time curve (AUC) compared with olanzapine 10 mg alone. An open-label, randomised, two-period, cross-over, single-centre trial was conducted in 24 healthy volunteers. Subjects were randomised to one of the following treatments: (A) fosamprenavir/ritonavir 700/100 mg twice daily (b.i.d.) for 16 days with a single dose of olanzapine 15 mg on Day 13, a wash-out period of 31 days and a single dose of olanzapine 10 mg on Day 48; or (B) the same medication in reverse order. Twenty subjects completed the trial. The geometric mean ratios (90% CI) of olanzapine AUClast, maximum drug concentration (C(max)) and apparent elimination half-life (t(1/2)) when taken with fosamprenavir/ritonavir versus olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74), respectively. Fosamprenavir/ritonavir 700/100 mg b.i.d. appeared to induce olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine when combining with a ritonavir-boosted protease inhibitor. PMID:24929949

  12. Functional and morphological changes in pig skin after single or fractionated doses in x rays

    SciTech Connect

    Young, C.M.A.; Hopewell, J.W.

    1982-09-01

    The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups.

  13. Efficacy of single dose epidural morphine versus intermittent low-dose epidural morphine along with bupivacaine for postcaesarean section analgesia

    PubMed Central

    Agarwal, Kiran; Agarwal, Navneet; Agrawal, V. K.; Agarwal, Ashok; Sharma, Mahender

    2012-01-01

    Background: Obstetric anesthesia presents a challenge to the anesthesiologist. The effective pain management allows the partu-rient adequate degree of comfort and promotes physical reco-very and a sense of well being. Materials and Methods: This randomized controlled study was designed to assess the analgesic efficacy and side effects of 1.20 mg single-dose epidural morphine (Group 1) versus intermittent 12 hourly epidural morphine (0.5 mg) with bupivacaine (Group2) for postoperative analgesia in lower segment caesarean section cases. Results: Each group consisted of 36 patients. Demographic characteristics of two groups were comparable and differences among them were not statistically significant. Mean duration of analgesia was significantly longer in group one patients (16.5±2.5h) in comparison to group two patients (11.5±1.5h). Mean highest visual analog scales (VAS scale) was significantly lower (3.2±0.9) in group one patients in comparison of group two (6.7±0.8) patients. Only 43% patient in group one required supplementary perenteral analgesic (Paracetamole/Diclofenac) and 71% required epidural morphine/bupivacaine in group two. Mean number of supplementary perenteral analgesic required in group one was 0.7 and it was 1.8 in group two. There was no significant difference in nausea, vomiting, itching, and pruritis in two groups of patients. Conclusion: Our study showed that the use of single dose epidural morphine is associated with lower pain scores at rest and movement when compared to intermittent epidural morphine with bupivacaine in postcaesarean section analgesia. PMID:25885497

  14. Single Dose of Levofloxacin versus Three Dosages for Prophylaxis in Prostate Biopsy

    PubMed Central

    Linden-Castro, Edgar; Pelayo-Nieto, Marcela; Alias-Melgar, Alejandro; Carreño-de la Rosa, Fernando

    2014-01-01

    Transrectal ultrasound-guided core prostate biopsy is a key event in the diagnosis of prostate cancer, transient side events such as local pain, haematuria, haematospermia, dysuria, and rectal bleeding are reported in a large number of patients. Antimicrobial agents lower the incidence of postbiopsy infectious complications. The timing and duration of the regimen and the route of administration remain controversial. We developed a standard prophylactic regimen, in which safety and efficiency were maximized, while costs and variability were minimized. Accordingly we prospectively evaluated 425 consecutive patients, who underwent outpatient transrectal ultrasound-guided prostate biopsy after a single dose versus three doses of levofloxacin.

  15. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

    PubMed Central

    Wu, Guolan; Zheng, Yunliang; Zhou, Huili; Hu, Xingjiang; Liu, Jian; Zhai, You; Zhu, Meixiang; Wu, Lihua; Shentu, Jianzhong

    2015-01-01

    Background Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. Methods A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. Results Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration– time curve from 0 to 10 hours (AUC0–10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. Conclusion Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10

  16. Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults

    PubMed Central

    Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

    2014-01-01

    Background Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis

  17. Single-dose ciprofloxacin at 100 versus 250 mg for treatment of uncomplicated urinary tract infections in women.

    PubMed Central

    Garlando, F; Rietiker, S; Täuber, M G; Flepp, M; Meier, B; Lüthy, R

    1987-01-01

    Two single-dose regimens of ciprofloxacin, 100 and 250 mg, were compared in the treatment of uncomplicated urinary tract infections in women. Cure rates 5 days after therapy did not significantly differ, being 16 of 19 (84%) with the 100-mg dose and 17 of 19 (89%) with the 250-mg dose. Ciprofloxacin was well tolerated. PMID:3551837

  18. Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

    PubMed Central

    Khalil, Eltahir A. G.; Weldegebreal, Teklu; Younis, Brima M.; Omollo, Raymond; Musa, Ahmed M.; Hailu, Workagegnehu; Abuzaid, Abuzaid A.; Dorlo, Thomas P. C.; Hurissa, Zewdu; Yifru, Sisay; Haleke, William; Smith, Peter G.; Ellis, Sally; Balasegaram, Manica; EL-Hassan, Ahmed M.; Schoone, Gerard J.; Wasunna, Monique; Kimutai, Robert; Edwards, Tansy; Hailu, Asrat

    2014-01-01

    Background Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. Methodology A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. Principal Findings The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. Conclusions The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. Trials Registration www.clinicaltrials.gov NCT00832208 PMID:24454970

  19. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    SciTech Connect

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-07-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation.

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

    PubMed Central

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

    2014-01-01

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

  1. The pharmacokinetics of a single intramuscular dose of amikacin in red-tailed hawks (Buteo jamaicensis).

    PubMed

    Bloomfield, R B; Brooks, D; Vulliet, R

    1997-03-01

    The pharmacokinetic parameters of amikacin were determined in red-tailed hawks (Buteo jamaicensis) following the i.m. administration of a single 20 mg/kg dose. After a rapid absorption phase, mean amikacin serum concentrations peaked at 65 +/- 12 micrograms/ML 30-45 min following injection. The serum amikacin concentrations decreased to 2.3 +/- 2 micrograms/ml at 12 hr postinjection. Amikacin was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.02 +/- 0.63 hr. The volume of distribution was estimated to be 0.28 +/- 0.03 L/kg. Forty-two isolates of gram-negative bacteria and coagulase-positive Staphylococcus species were cultured from birds of prey presented to the Veterinary Medical Teaching Hospital at the University of California-Davis. The minimum inhibitory concentration (MICs) of amikacin ranged from 0.5 to 8.0 micrograms/ml (mean = 2.5 micrograms/ml). The 20 mg/kg dose used in this study resulted in serum concentrations at or above the MICs for > 12 hr for most of the isolates examined. The heaviest birds had the lowest peak serum amikacin concentrations, and the lightest birds had the highest, despite exact volume replacement for each sample drawn. This observation suggests that doses should be based on factors other than weight alone. Amikacin administered at 15-20 mg/kg/day, either as a single dose or divided into two or three doses, is effective in treating sensitive pathogens of the red-tailed hawk. PMID:9226617

  2. Single-dose Intramuscular Injection Toxicology of Danggui Pharmacopuncture (DGP) in Sprague-Dawley Rats

    PubMed Central

    Sun, SeungHo; Jeong, JongJin; Park, Sunju; Lee, KwangHo; Yu, JunSang; Seo, Hyung-Sik; Kwon, KiRok

    2015-01-01

    Objectives: The purpose of the study is to assess both the approximate lethal dose and the single dose intramuscular injection toxicity of Danggui (Angelica gigantis radix) pharmacopuncture (DGP) in Sprague-Dawley (SD) rats. Methods: The experiments were conducted at the good laboratory practice (GLP) laboratory, Biotoxtech Co., which is a laboratory approved by the ministry of food and drug safety (MFDS). The study was performed according to the GLP regulation and the toxicity test guidelines of the MFDS (2009) after approval of the institutional animal care and use committee of Biotoxtech. Single doses of DGP were injected intramuscularly into the rats in three test groups of 6 week old SD rats (5 male and 5 female rats per groups) in the amounts of 0.1, 0.5, and 1.0 mL/animal for groups 2, 3, and 4, respectively, and normal saline solution in the amount of 1.0 mL/animal was injected intramuscularly into the rats (5 male and 5 female rats) in the control group. Observations of the general symptoms and weight measurements were performed during the 14 day observation period after the injection. Hematologic and serum biochemical examination, necropsy, and a local tolerance test at the injection site were done after the observation period. Results: No death was observed in three test groups (0.1, 0.5 and 1.0 mL/animal group). In addition, the injection of DGP had no effect on general symptoms, weights, hematologic and serum biochemical examination, and necropsy. The results from the local tolerance tests at injection site showed no treatment related effects in the SD rats. Conclusion: The results of single dose intramuscular injection of DGP suggest that the approximate lethal dose is above 1.0 mL/animal for both male and female SD rats and that intramuscular injection of DGP may be safe. PMID:25830059

  3. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge.

    PubMed

    Mallajosyula, Jyothi K; Hiatt, Ernie; Hume, Steve; Johnson, Ashley; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P; Bratcher, Barry; Haydon, Hugh; Webby, Richard J; McCormick, Alison A

    2014-01-01

    Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15 µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein. PMID:24378714

  4. Single high-dose vs. fractionated radiotherapy: Effects on plant growth rates

    PubMed Central

    Guedea, Marc; Castel, Antoni; Arnalte, Marc; Mollera, Alex; Muñoz, Victor; Guedea, Ferran

    2013-01-01

    Aim To evaluate the differential effects of fractionated vs. high-dose radiotherapy on plant growth. Background Interest in hypofractionated radiotherapy has increased substantially in recent years as tumours (especially of the lung, prostate, and liver) can be irradiated with ever greater accuracy due to technological improvements. The effects of low-dose ionizing radiation on plant growth have been studied extensively, yet few studies have investigated the effect of high-dose, hypofractionated radiotherapy on plant growth development. Materials and methods A total of 150 plants from the genus Capsicum annuum were randomized to receive fractionated radiotherapy (5 doses of 10 Gy each), single high-dose (SHD) radiotherapy (single 50 Gy dose), or no radiotherapy (control group). Irradiation was delivered via linear accelerator and all samples were followed daily for 26 days to assess and compare daily growth. Results On day 26, plants in the control, fractionated, and SHD groups had grown to a mean height of 7.55 cm, 4.32 cm, and 2.94 cm, respectively. These differences in overall growth were highly significant (P = 0.005). The SHD group showed the least amount of growth. Conclusions SHD effectively stunts plant growth and development. Despite the evident differences between plant and animal cells, ionizing radiation is believed to work in a similar manner in all biological cells. These findings highlight the need to continue investigating the use of hypofractionated schemes in humans to improve cancer treatment outcomes. PMID:24416565

  5. Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

    PubMed

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick

    2010-06-01

    To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety. PMID:20806657

  6. Ultrastructural effects of albendazole on the body wall of Gnathostoma spinigerum third stage larvae.

    PubMed

    Arunyanart, Channarong; Kanla, Pipatphong; Chaichun, Amnart; Intapan, Pewpan M; Maleewong, Wanchai

    2009-11-01

    This study investigated the effects of albendazole (ABZ) on the ultrastructure of Gnathostoma spinigerum advanced third-stage larvae. Two groups of experimentally infected mice received 60 or 90 mg/kg ABZ orally once a day for 21 consecutive days. Both groups had damage to the body walls of the worms, especially to the non-contractile part of the muscular layer. The severity of the damage was dose related, the higher the dose, the greater the damage. The body wall of the ABZ treated larvae demonstrated a decrease in the number of mitochondria in the non-contractile muscular part, especially in the internal surface of the sarcolemma. Some mitochondria developed large vacuoles, and became distorted and degenerated. The nuclei degenerated and had irregular shapes and the number of glycogen granules decreased. The present study demonstrates the structural damage induced by the toxic effects of ABZ and increases our knowledge of the mechanism of action of ABZ against G. spinigerum. PMID:20578453

  7. Efficacy of an anthelmintic combination in sheep infected with Fasciola hepatica resistant to albendazole and clorsulon.

    PubMed

    Martínez-Valladares, M; Cordero-Pérez, C; Rojo-Vázquez, F A

    2014-01-01

    In the current study, we identified five sheep flocks with fasciolosis in the province of León (northwestern Spain) in order to determine the anthelmintic resistance status to three commonly used anthelmintics, namely albendazole (ABZ), triclabendazole (TCBZ) and clorsulon (CLOR). The identification of one flock resistant to ABZ and CLOR was shown after the faecal egg count reduction test (FECRT). The reductions in eggs per gram values were -17.6% and -68% against immature and adult flukes, respectively, after ABZ treatment; 85.15% and 44.91% against immature and adult flukes, respectively, after CLOR treatment; and 97.06% against both stages, after the administration of TCBZ. As an alternative to control the infection, two combinations of ABZ and CLOR were tested. In the first, both drugs were administered at the recommended dose of each; in this case, the efficiency reached values above 95% against both immature and adult flukes. However, when the combined drugs were administered at half the recommended dose of each, the efficiency of the combination was very low, i.e. 16.67% and -11.11% against mature and immature flukes, respectively. In conclusion, this preliminary report suggests a possible interaction between ABZ and CLOR after their joint administration. However, these results should be confirmed in other flocks. PMID:24211419

  8. Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations.

    PubMed

    Ceballos, Laura; Elissondo, Celina; Moreno, Laura; Dopchiz, Marcela; Sánchez Bruni, Sergio; Denegri, Guillermo; Alvarez, Luis; Lanusse, Carlos

    2008-07-01

    The pharmacokinetic (PK) behaviour and clinical efficacy of albendazole (ABZ) against hydatid cysts in mice were assessed after treatment with two different ABZ pharmaceutical formulations. BalbC mice received ABZ (0.5 mg/kg) prepared either as solution or suspension (50 microg/ml) for oral administration (PK study). Blood samples were collected up to 16 h post-treatment and processed to measure ABZ/metabolites concentrations in plasma. The clinical efficacy assessment was performed in BalbC mice infected 8 months earlier with Echinococcus granulosus protoscoleces. Infected animals were allocated into three experimental treatment groups: (a) untreated control, (b) ABZ-solution treated, (c) ABZ-suspension treated. Both treated groups received ABZ (0.5 mg/kg) administered under two different therapeutic schemes: dosing every 48 h over 30 days (regimen I) or treated every 12 h during 15 days (regimen II). Experimental mice were sacrificed 12 h after treatment, and cysts were recovered, weighed and processed for transmission electron microscopy. Enhanced ABZ sulphoxide (the main ABZ metabolite) concentration profiles were measured in animals treated with the ABZ solution. Any positive clinical response was obtained after treatment every 48 h (30 days therapy). However, consistent with the observed PK results, both ABZ formulations were clinically effective in infected mice treated with a 12-h dosing interval (15 days therapy). PMID:18465143

  9. Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

    SciTech Connect

    Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G. )

    1991-03-01

    The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor.

  10. Induction of lymphoma and osteosarcoma in mice by single and protracted low alpha doses

    SciTech Connect

    Mueller, W.A.L.; Luz, A.; Murray, A.B.; Linzner, U. )

    1990-09-01

    Internal doses from the short-lived alpha-emitter 22Ra were given to 4-wk-old female mice. One group of about 300 animals received a single injection of 18.5 kBq 22Ra kg-1 body weight, corresponding to a mean skeletal alpha dose of 0.15 Gy. A second group of about 300 animals received the same total amount of 224Ra in the form of 72 fractions of 257 Bq kg-1 each, applied twice weekly during 36 wk. The fractionated group received the same final mean total skeletal dose of 0.15 Gy as the single injected group, but with a mean skeletal dose rate of 1 mGy d-1. A rather high incidence, 13.5% (40/296), of early malignant lymphomas was observed in the fractionated group during and shortly after the injection period, followed by a 7% incidence (21/296) of osteosarcomas during the second half of the animals' lifetime. The group with a single injection did not develop early lymphomas but did develop osteosarcomas later with an incidence of 5.8% (17/295). The occurrence of osteosarcomas was similar up to day 800 in the two experimental groups. Surprisingly, however, after this period no additional case of osteosarcoma was observed in the single-injected group, whereas one-third of all osteosarcomas occurred after day 800 in the protracted group. The additional later occurrence of osteosarcomas occurred after indicates a longer lasting induction effect on osteosarcomas, or a promoting effect in older age, for this kind of treatment.

  11. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    PubMed

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-01-01

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

  12. Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria.

    PubMed

    Tun, Thein; Tint, Hla Soe; Lin, Khin; Kyaw, Thar Tun; Myint, Moe Kyaw; Khaing, Win; Tun, Zaw Win

    2009-09-01

    All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment. PMID:19464245

  13. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

    PubMed Central

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi

    2015-01-01

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

  14. Persistence of Immunity Acquired after a Single Dose of Rubella Vaccine in Japan.

    PubMed

    Okafuji, Takao; Okafuji, Teruo; Nakayama, Tetsuo

    2016-05-20

    To date, Takahashi, Matsuura, and TO-336 strains of live-attenuated rubella vaccine have been used in Japan. Japan implemented a single-dose rubella vaccination program until 2006. However, few reports are available on the persistence of immunity after this vaccination program. We collected 276 serum samples from January 2009 to December 2011 at Okafuji Pediatric Clinic and assessed the immune status of these samples against rubella virus during 1-10 years after vaccination with a single dose of Takahashi rubella vaccine. Regional outbreak of rubella did not occur during 1999-2011. The collected serum samples were tested for antibodies against the rubella virus by performing a standard hemagglutination inhibition (HAI) test. Our results showed that all the tested serum samples contained antibodies against the rubella virus 10 years after the vaccination. Geometric mean titer of HAI antibodies was 1:180 and decreased to 1:68 at 10 years after the vaccination. The levels of HAI antibodies decreased logarithmically with time after the vaccination. In conclusion, vaccine-acquired immunity after vaccination with a single dose of live-attenuated Takahashi rubella vaccine was retained for at least 10 years when rubella was under regional control. PMID:26255735

  15. Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls.

    PubMed

    Hahn, Margaret Karolina; Wolever, Tom M S; Arenovich, Tamara; Teo, Celine; Giacca, Adria; Powell, Valerie; Clarke, Leigh; Fletcher, Paul; Cohn, Tony; McIntyre, Roger S; Gomes, Sylvia; Chintoh, Araba; Remington, Gary J

    2013-12-01

    Atypical antipsychotics may "directly" influence glucose homeostasis, increasing risk of type 2 diabetes independently of changes in adiposity. Animal models suggest direct effects after even a single dose of certain atypical antipsychotics on glucose dysregulation. Here, we investigated effects of a single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby minimizing confounding effects of the illness of schizophrenia and adiposity. In a randomized double-blind crossover design, 15 subjects were administered 10 mg of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled intravenous glucose tolerance test was initiated 4.25 hours later to assess changes in glucose homeostasis, including an index of insulin sensitivity, disposition index, glucose effectiveness, and acute insulin response to glucose. We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs), insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C-reactive protein, interleukin 6, and tumor necrosis factor α). Complete data for both visits were analyzed for 12 subjects. Olanzapine treatment significantly decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25 hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may invoke early changes in some parameters of glucose and lipid metabolism, as well as endocrine indices. PMID:24100786

  16. A single subcutaneous dose of tramadol for mild to moderate musculoskeletal trauma in the emergency department

    PubMed Central

    Cardozo, Alejandro; Silva, Carlos; Dominguez, Luis; Botero, Beatriz; Zambrano, Paulo; Bareno, Jose

    2014-01-01

    BACKGROUND: Mild to moderate musculoskeletal trauma is a common cause for an emergency room visit, and frequent pain is one of the cardinal symptoms of consultation. The objective of this study is to assess the perception of a single subcutaneous dose of 50 mg tramadol for pain management in patients with mild to moderate musculoskeletal trauma, likewise to appraise the perception of pain by subcutaneous injection. METHODS: A total of 77 patients, who met inclusion criteria, received a single subcutaneous dose of tramadol. Pain control was evaluated based on the verbal numerical pain scale (0–10) at baseline, 20 and 60 minutes; similarly, pain perception was evaluated secondary to subcutaneous injection of the analgesic. RESULTS: On admission, the average pain perceived by patients was 8; twenty minutes later, 89% of the patients reported five or less, and after sixty minutes, 94% had three or less on the verbal numerical pain scale. Of the patients, 88% reported pain perception by verbal numeric scale of 3 or less by injection of the drug, and 6.5% required a second analgesic for pain control. Two events with drug administration (soft tissue infection and mild abdominal rectus injection) were reported. CONCLUSION: We conclude that a single subcutaneous dose of tramadol is a safe and effective option for the management of patients with mild to moderate pain and musculoskeletal disease in the emergency department. PMID:25548601

  17. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

    PubMed Central

    Castro, Silvina G.; Dib, Alicia; Suarez, Gonzalo; Allemandi, Daniel; Lanusse, Carlos; Sanchez Bruni, Sergio; Palma, Santiago D.

    2013-01-01

    The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form. PMID:24063016

  18. Beyond Gaussians: a study of single-spot modeling for scanning proton dose calculation

    NASA Astrophysics Data System (ADS)

    Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

    2012-02-01

    Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field size effects on dose output. In this study, we developed a pencil beam algorithm for scanning proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy

  19. Beyond Gaussians: a study of single spot modeling for scanning proton dose calculation

    PubMed Central

    Li, Yupeng; Zhu, Ronald X.; Sahoo, Narayan; Anand, Aman; Zhang, Xiaodong

    2013-01-01

    Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field-size effects on dose output. In the present study, we developed a pencil-beam algorithm for scanning-proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil-beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field-size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID:22297324

  20. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    SciTech Connect

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED/sub 50/ dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and ..gamma..-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED/sub 50/ dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair, and even at the highest LET investigated (neon ions in

  1. Application of optically stimulated luminescence technique to evaluate simultaneously accumulated and single doses with the same dosimeter

    NASA Astrophysics Data System (ADS)

    Malthez, Anna Luiza M. C.; Freitas, Marcelo B.; Yoshimura, Elisabeth M.; Button, Vera L. S. N.

    2014-02-01

    Optically stimulated luminescence dosimeters (OSLD) can be read several times with a negligible loss (degradation) of signal. In this work, we explore this OSL property to estimate simultaneously the accumulated and single doses using a unique Al2O3 dosimeter, irradiated repeated times along over 4 months. This was done through several irradiations of OSLD (Landauer Luxel Dots) with two energies (28 keV X-rays and 1.25 MeV Co-60 gamma rays) and several doses distributed over time. Thermoluminescent dosimeters (TLD) were used as a reference to compare the estimated doses obtained with OSLD. For each irradiation, and both energies, a calibration curve was evaluated with OSLD and TLD to estimate the dose values. The OSL readouts were made with a MicroStar (Landauer) OSL reader. To estimate background (BG) over time, a set of OSLD and TLD (Bycron TLD100) was not irradiated and BG was monitored at each readout section. After irradiations, the OSL and TL signals were converted to dose and values were compared. As a set of OSLD suffered no bleaching after the readouts, it was possible to estimate simultaneously the accumulated and single doses with a unique OSLD. Each single dose was estimated through the subtraction of successive accumulated doses determined for each single OSLD. We concluded that the single doses determined by OSL and TL techniques were compatible, and that the accumulated dose, obtained with OSL technique was comparable to the sum of single doses determined with TLD. We can conclude that using OSL technique and Al2O3 dosimeters it is possible to estimate simultaneously accumulated and single doses with the same dosimeter irradiated with low or high energy photons.

  2. Single- and repeated-dose toxicities of aloe fermentation products in rats

    PubMed Central

    Kim, Hyun-Kyoung; Baik, Soon-Ok; Choi, Soo-Young; Lee, Jae-Young

    2011-01-01

    In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. β-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity. PMID:21998613

  3. Pharmacokinetics of single-dose primaquine in patients with chronic kidney dysfunction

    PubMed Central

    Kulkarni, Shaunak P.; Shah, Sanjana R.; Kadam, Prashant P.; Sridharan, Kannan; Hase, Nivrutti K.; Shetty, Partha P.; Thatte, Urmila M.; Gogtay, Nithya J.

    2013-01-01

    Aim: The pharmacokinetics of primaquine has not been studied in special populations. Being a basic compound, preferential binding to alpha-1 acid glycoprotein and substrate for P-glycoprotein, may predispose the drug for an altered pharmacokinetics in states of renal dysfunction. This study attempts to evaluate the pharmacokinetics of a single oral dose (15 mg) of primaquine in severely impaired renal function and end stage renal dysfunction patients compared to healthy participants. Materials and Methods: Twelve patients each with chronic kidney disease classified as either Stage IV or V (not on dialysis) were recruited. Data from 12 healthy participants was used as concurrent controls. Serial blood collections were performed following a single dose 15 mg Primaquine orally. Primaquine concentrations were measured in the plasma using a validated HPLC method. Results: The Cmax [median (range) in ng/ml] was 29.3 (14.6-104.3), 40.3 (14.8 - 78.6), and 49.8 (15 – 169.6) and the tmax [median (range) in hours] was 3.0 (1.0- 6.0), 2.0 (1.5 – 8) and 2.0 (1.0 – 4.0) for healthy and stage IV, V (not on dialysis) CKD participants, respectively. No statistically significant difference was observed in any of the pharmacokinetic parameters between healthy, stage IV and V CKD participants. Conclusion: Pharmacokinetics of single oral dose primaquine (15 mg) does not appear to be altered in patients with severely impaired renal function and end stage renal dysfunction. A change in dose or frequency of the drug administration perhaps may not be required in this population. PMID:24014905

  4. Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing

    PubMed Central

    De Wilde, J. E.; Mertens, C.; Wakelin, J. S.

    1983-01-01

    1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar or bipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (± s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (± s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (± s.d. 22.3) improvement for fluvoxamine and 62.1% (± s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine. PMID:6407503

  5. Treatment of Chronic Spontaneous Urticaria with a Single Dose of Omalizumab: A Study of Four Cases

    PubMed Central

    Subramaniyan, Radhakrishnan; Chopra, Ajay

    2016-01-01

    Background: Chronic spontaneous urticaria (CSU) has a detrimental effect on patients’ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI). Results: A sharp decline in UAS7 and DLQI was documented in 7–10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy. PMID:27512204

  6. Single-dose pharmacokinetics of indinavir and the effect of food.

    PubMed

    Yeh, K C; Deutsch, P J; Haddix, H; Hesney, M; Hoagland, V; Ju, W D; Justice, S J; Osborne, B; Sterrett, A T; Stone, J A; Woolf, E; Waldman, S

    1998-02-01

    Indinavir sulfate is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor indicated for treatment of HIV infection and AIDS in adults. The purpose of this report is to summarize single-dose studies which characterized the pharmacokinetics of the drug and the effect of food in healthy volunteers. Indinavir concentrations in plasma and urine were obtained by high-pressure liquid chromatography and UV detection assay methods. The results indicate that indinavir was rapidly absorbed in the fasting state, with the time to the maximum concentration in plasma occurring at approximately 0.8 h for all doses studied. Over the 40- to 1,000-mg dose range studied, concentrations in plasma and urinary excretion of unchanged drug increased greater than dose proportionally. The nonlinear pharmacokinetics were attributed to the dose-dependent oxidative metabolism of first-pass metabolism as well as to metabolism in the systemic circulation. Renal clearance slightly exceeded the glomerular filtration rate, suggesting a net tubular secretion component. At high concentrations in plasma, tubular secretion appeared to be lowered because there was a trend for a decreased renal clearance. Administration of 400 mg of indinavir sulfate following a high-fat breakfast resulted in a blunted and decreased absorption (areas under the concentration-time curves [AUCs], 6.86 microM.h in the fasted state versus 1.54 microM.h in the fed state; n = 10). However, two types of low-fat meals were found to have no significant effect on the absorption of 800 mg of indinavir sulfate (AUCs, 23.15 microM.h in the fasted state versus 22.71 and 21.36 microM.h, respectively, in the fed state; n = 11). Immediately following dosing, the concentrations of indinavir in urine often exceeded its intrinsic solubility. To reduce the risk of nephrolithiasis, it is recommended that indinavir sulfate be administered with water. PMID:9527781

  7. Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

    SciTech Connect

    Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

    2012-08-01

    Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher's exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade {>=}3 acute or late toxicity was 6.8% (14 patients). Fisher's exact test resulted in significant median splits for grade {>=}3 toxicity at V12 = 3.78 cm{sup 3} (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm{sup 3} (RR 13, P=.0013), V20 = 0.11 cm{sup 3} (RR 6, P=0.01), and V22 = 0.0 cm{sup 3} (RR 13, P=.0013). The median split for D2.5 cm{sup 3} (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm{sup 3}. One hundred percent (n = 7) of grade {>=}4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade {>=}3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation

  8. Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

    SciTech Connect

    Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

    2015-10-01

    Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

  9. Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares.

    PubMed

    Wong, D M; Davis, J L; Alcott, C J; Hepworth-Warren, K L; Galow-Kersh, N L; Rice, S; Coetzee, J F

    2015-06-01

    The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted. PMID:25427652

  10. Comparative disposition of codeine and pholcodine in man after single oral doses.

    PubMed Central

    Findlay, J W; Fowle, A S; Butz, R F; Jones, E C; Weatherley, B C; Welch, R M; Posner, J

    1986-01-01

    Four healthy male subjects received single oral doses of 15, 30 and 60 mg of codeine and pholcodine according to a balanced cross-over design with an interval of 7 days between the six treatments. Blood samples were collected for 8 h after each drug administration. In phase 2 of the study six different male volunteers received single oral doses of 60 mg of codeine and pholcodine with a 14 day interval between successive drug treatments. Blood was sampled for 12 h after codeine and 121 h after pholcodine administration. Plasma concentrations of free (unconjugated) and total (unconjugated plus conjugated) codeine, pholcodine and morphine were determined by radioimmunoassay and selected pharmacokinetic parameters were derived from these data. Pharmacokinetics of both drugs were independent of dose. Codeine was absorbed and eliminated relatively rapidly [elimination t1/2 = 2.3 +/- 0.4 h (mean +/- s.d.)]. While codeine kinetics were adequately described by a one-compartment open model with first-order absorption, a two-compartment model was required to describe pholcodine elimination from plasma (t1/2,z = 37.0 +/- 4.2 h). Plasma concentrations of conjugated codeine were much greater than those of the unconjugated alkaloid. By contrast, pholcodine appeared to undergo little conjugation. Biotransformation of codeine to morphine was evident in all subjects, although the extent of this metabolic conversion varied considerably between subjects. Morphine was not detectable in the plasma of any subject after pholcodine administration. PMID:3741728

  11. Evidence for CVD 103-HgR as an effective single-dose oral cholera vaccine.

    PubMed

    Jackson, Sarah S; Chen, Wilbur H

    2015-01-01

    We propose the ideal oral cholera vaccine (OCV) should be an inexpensive, single, oral dose that rapidly confers immunity for a long duration, and is well tolerated by individuals vulnerable to cholera. Vaccine trials in industrialized countries of a single oral dose of 5 × 10(8) colony forming units (CFU) of the live, attenuated cholera strain CVD 103-HgR have shown 88-97% serum vibriocidal antibody seroconversion rates, a correlate of protection and documented vaccine efficacy of ≥80% using volunteer challenge studies with wild-type cholera. For individuals of developing countries, a 5 × 10(9) CFU dose of CVD 103-HgR is necessary to elicit similar antibody responses. Presently, a reformulation of CVD 103-HgR is in late-stage clinical development for prospective US FDA licensure; making a cholera vaccine for US travelers potentially accessible in 2016. The availability of CVD 103-HgR should be a welcome addition to the currently available OCVs. PMID:26228388

  12. Single dose toxicity study of IRDye 800CW in Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Marshall, Milton V.; Draney, Daniel; Sevick-Muraca, Eva M.; Olive, D. Michael

    2010-02-01

    Fluorophore-labeled contrast imaging agents are moving toward clinical use as aids in nodal staging and intraoperative resection of tumors. Near-infrared fluorophores with defined toxicity properties will be needed before these agents can be translated to the clinic. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. We report here the results of a preliminary toxicity study on IRDye 800CW carboxylate in preparation for its use as a labeling moiety for targeted contrast agents. Male and female Sprague Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; indocyanine green was used as a comparative control. Following administration of varying doses of either the dyes or saline, animals were observed for up to fourteen days during which time, hematological, clinical chemistry, enzymological, and histological testing was performed on animal subgroups. Under the conditions tested, a single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5 and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. A dose of 20 mg/kg was identified as the NOAEL (no observed adverse effect level) following IV or ID routes of administration of IRDye 800CW.

  13. Pharmacokinetics of a single subcutaneous dose of sustained release buprenorphine in northern elephant seals (Mirounga angustirostris).

    PubMed

    Molter, Christine M; Barbosa, Lorraine; Johnson, Shawn; Knych, Heather K; Chinnadurai, Sathya K; Wack, Raymund F

    2015-03-01

    Information regarding analgesics in pinnipeds is limited. This study aimed to establish the pharmacokinetic parameters of a single subcutaneous dose of sustained release buprenorphine (Buprenorphine SR) in juvenile northern elephant seals (Mirounga angustirostris) with regard to its potential to provide long-lasting analgesia that requires infrequent dosing. Seals (n=26) were administered a single dose of sustained release buprenorphine at 0.12 mg/kg s.c. Blood samples were collected from the extradural intervertebral vein at 0 hr and at three or four of the following time points: 0.5, 1, 2, 6, 12, 24, 36, 48, 60, 96, 120, and 144 hr. Seals were examined daily for systemic and local adverse reactions. Plasma was analyzed by liquid chromatography tandem-mass spectrometry for buprenorphine and norbuprenorphine concentrations. A noncompartmental analysis for pharmacokinetic parameters was calculated using standard methods and equations. An average maximum concentration of 1.21 ng/ml (0.3-2.9 ng/ml) was detected 12 hr postadministration. Concentrations were quantifiable up to 144 hr postadministration but were below those expected to provide analgesia in some other species. No systemic adverse effects were noted in healthy seals receiving sustained release buprenorphine. Cellulitis or abscesses at the injection site were observed in 6/26 (23%) seals between 24 and 168 hr postadministration. Adverse local effects suggest that this drug should be used with caution in northern elephant seals. PMID:25831576

  14. Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

    PubMed

    Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

    2011-12-01

    The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively. PMID:24278575

  15. Single Oral Dose Toxicity Test of Platycodin D, a Saponin from Platycodin Radix in Mice

    PubMed Central

    Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang

    2011-01-01

    The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively. PMID:24278575

  16. Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study

    PubMed Central

    Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.

    2013-01-01

    Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with

  17. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    PubMed Central

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  18. Two novel ternary albendazole-cyclodextrin-polymer systems: dissolution, bioavailability and efficacy against Taenia crassiceps cysts.

    PubMed

    Palomares-Alonso, Francisca; González, Cesar Rivas; Bernad-Bernad, Ma Josefa; Montiel, María Dolores Castillo; Hernández, Guadalupe Palencia; González-Hernández, Iliana; Castro-Torres, Nelly; Estrada, Enrique Pinzón; Jung-Cook, Helgi

    2010-01-01

    The effect of two water-soluble polymers: pectin and polyvinylpyrrolidone in combination with beta-cyclodextrin, on the dissolution, bioavailability and cysticidal efficacy of albendazole was evaluated using a commercial suspension as reference product. The dissolution of the albendazole-beta-cyclodextrin-pectin formulation was slow and incomplete (44.7%). No statistical differences in C(max) and AUC were found between this formulation and the reference. Also its cysticidal efficacy (33%) was similar to the reference (38%). The albendazole-beta-cyclodextrin-polyvinylpyrrolidone formulation exhibited the highest dissolution rate (78.5%) and its bioavailability was also significantly increased (2.3-fold). In addition, the cysticidal activity of this formulation (83%) was greater than a commercial suspension. Our results suggest that the ternary system of albendazole-beta-cyclodextrin-polyvinylpyrrolidone could be a potential alternative for the treatment of systemic helmintic diseases and it is worth to continue its preclinical evaluation. PMID:19769931

  19. Comparative Analysis of Efficacy and Safety of Multisession Radiosurgery to Single Dose Radiosurgery for Metastatic Brain Tumors

    PubMed Central

    Lee, Gwang Soo; Kim, Ji Hoon; Park, Hyung Ki; Park, Suk Que; Kim, Ra Sun; Jang, Jae Chil

    2015-01-01

    Background The purpose of this study is to compare the efficacy and safety of multisession radiosurgery to those of single dose radiosurgery for metastatic brain tumors. Methods Between February 2008 and February 2012, 90 patients with 196 metastatic brain tumors were treated with cyberknife radiosurgery, and we reviewed these patients retrospectively. Among them, 57 patients underwent single dose radiosurgery, and 33 patients multisession radiosurgery. Tumors involving the eloquent area and large tumors (>5 cc) were treated with multisession radiosurgery. The median tumor volume and the median treatment dose of single dose radiosurgery were 2.05±0.72 cc and 19.76±1.54 Gy respectively, and in the case of multisession radiosurgery, 5.30±1.70 cc and 29.6±1.70 Gy respectively. The frequency of multisession dose was 3 to 5 times, on average 3.55 times, and 8.91 Gy were given per 1 session on average. Results The overall survival (OS) of multisession radiosurgery was 16.0 months, whereas that of single dose radiosurgery was 11.5 months. The radiologic tumor response rates were 90% in single dose radiosurgery and 95.4% in multisession radiosurgery, respectively. Over 6-month and 1-year periods, the OS rates of single dose radiosurgery were 71.4% and 44.9%, whereas those of multisession radiosurgery were 69.1% and 58.3%, respectively (p=0.83). Toxicities were seen in 18.1% in the single dose radiosurgery group versus 4% in the multisession radiosurgery group. The difference was significant (p<0.05). Conclusion In this study, the multisession radiosurgery group, despite the location and size constraints, did not differ from the single dose radiosurgery group when comparing the survival and recurrence rates, but complications and toxicity were lower. Thus, multisession radiosurgery is thought to be beneficial for treatment of large tumors and tumors located in the eloquent area. PMID:26605264

  20. Continuous DOPA synthesis from a single AAV: dosing and efficacy in models of Parkinson's disease

    PubMed Central

    Cederfjäll, Erik; Nilsson, Nathalie; Sahin, Gurdal; Chu, Yaping; Nikitidou, Elisabeth; Björklund, Tomas; Kordower, Jeffrey H.; Kirik, Deniz

    2013-01-01

    We used a single adeno-associated viral (AAV) vector co-expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) to investigate the relationship between vector dose, and the magnitude and rate of recovery in hemi-parkinsonian rats. Intrastriatal injections of >1E10 genomic copies (gc) of TH-GCH1 vector resulted in complete recovery in drug-naïve behavior tests. Lower vector dose gave partial to no functional improvement. Stereological quantification revealed no striatal NeuN+ cell loss in any of the groups, whereas a TH-GCH1 dose of >1E11 gc resulted in cell loss in globus pallidus. Thus, a TH-GCH1 dose of 1E10 gc gave complete recovery without causing neuronal loss. Safety and efficacy was also studied in non-human primates where the control vector resulted in co-expression of the transgenes in caudate-putamen. In the TH-GCH1 group, GCH1 expression was robust but TH was not detectable. Moreover, TH-GCH1 treatment did not result in functional improvement in non-human primates. PMID:23831692

  1. Drug and light dose responses to focal photodynamic therapy of single blood vessels in vivo

    NASA Astrophysics Data System (ADS)

    Khurana, Mamta; Moriyama, Eduardo H.; Mariampillai, Adrian; Samkoe, Kimberley; Cramb, David; Wilson, Brian C.

    2009-11-01

    As part of an ongoing program to develop two-photon (2-γ) photodynamic therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD) and other vascular pathologies, we have evaluated the reciprocity of drug-light doses in focal-PDT. We targeted individual arteries in a murine window chamber model, using primarily the clinical photosensitizer Visudyne/liposomal-verteporfin. Shortly after administration of the photosensitizer, a small region including an arteriole was selected and irradiated with varying light doses. Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point metric, there was reciprocity between the drug and light doses, i.e., the response correlated with the drug-light product (DLP). These results provide the first quantification of photosensitizer and light dose relationships for localized irradiation of a single blood vessel and are compared to the DLP required for vessel closure between 1-γ and 2-γ activation, between focal and broad-beam irradiation, and between verteporfin and a porphyrin dimer with high 2-γ cross section. Demonstration of reciprocity over a wide range of DLP is important for further development of focal PDT treatments, such as the targeting of feeder vessels in 2-γ PDT of AMD.

  2. Comparative plasma disposition kinetics of albendazole and its new benzimidazol prodrug in dog.

    PubMed

    Khalil, Z; El Karbane, M; Faouzi, M E A; Ansar, M; Azougagh, M; El Harti, J; Taoufik, J

    2016-01-01

    The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug [1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl] (ABZBoc), following their oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0-›∞), and analyzed using the Student's t-test, P<0.05. Thus,the pharmacokinetic analysis indicated four statistically significant changes in the pharmacokinetic parameters defined above of the albendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs. PMID:26530448

  3. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic.

    PubMed

    Stein, A; Ben Dov, D; Finkel, B; Mecz, Y; Kitzes, R; Lurie, A

    1996-07-01

    A double-blind controlled study was designed to compare the effective- ness of a single intramuscular dose of 60 mg ketorolac with that of 75 mg diclofenac in the treatment of renal colic and to monitor side effects. Fifty-seven patients completed the study, 27 in the ketorolac group and 30 in the diclofenac group. Effectiveness of treatment was monitored by pain relief reported on a 4-point verbal scale at different time points. At 60 minutes 77.8% and 86.6% (P = 0.4) of patients, and at 120 minutes 81.5% and 96.6% (P = .1 5) of patients, reported significant pain relief following ketorolac and diclofenac doses, respectively. Both groups had an equal 92% significant pain relief at discharge from the emergency department. Both drugs were well tolerated by the patients. Ketorolac therefore, seems as effective as diclofenac in the treatment of renal colic. PMID:8768161

  4. Concentrations of cefpodoxime in plasma and pleural fluid after a single oral dose of cefpodoxime proxetil.

    PubMed

    Dumont, R; Guetat, F; Andrews, J M; Sultan, E; Lenfant, B

    1990-12-01

    Eighteen patients of either sex with pleural effusions underwent aspiration 3, 6 or 12 h after receiving a single oral dose of cefpodoxime proxetil equivalent to 200 mg cefpodoxime. The mean concentrations of cefpodoxime in pleural fluid were, respectively, 0.62, 1.84 and 0.78 mg/l for these three time intervals, the corresponding ratios between pleural fluid and plasma concentrations being 0.24, 0.67 and 1.07. The findings indicate that there is good penetration of cefpodoxime into pleural fluid. Concentrations between 3 and 12 h after dosing were equal to or above the MIC90 for most of the organisms commonly found in lower respiratory tract infections. PMID:2292529

  5. Comparative assessment of single-dose and fractionated boron neutron capture therapy

    SciTech Connect

    Coderre, J.A.; Micca, P.L.; Fisher, C.D.

    1995-12-01

    The effects of fractionating boron neutron capture therapy (BNCT) were evaluated in the intracerebral rat 9L gliosarcoma and rat spinal cord models using the Brookhaven Medical Research Reactor (BMRR) thermal neutron beam. The amino acid analog p-boronophenylalanine (BPA) was administered prior to each exposure to the thermal neutron beam. The total physical absorbed dose to the tumor during BNCT using BPA was 91% high-linear energy transfer (LET) radiation. Two tumor doses of 5.2 Gy spaced 48 h apart (n = 14) or three tumor doses of 5.2 Gy, each separated by 48 h (n = 10), produced 50 and 60% long-term (>1 year) survivors, respectively. The outcome of neither the two nor the three fractions of radiation was statistically different from that of the corresponding single-fraction group. In the rat spinal cord, the ED{sub 50} for radiation myelopathy (as indicated by limb paralysis within 7 months) after exposure to the thermal beam alone was 13.6 {+-} 0.4 Gy. Dividing the beam-only irradiation into two or four consecutive daily fractions increased the ED{sub 50} to 14.7 {+-} 0.2 Gy and 15.5 {+-} 0.4 Gy, respectively. Thermal neutron irradiation in the presence of BPA resulted in an ED{sub 50} for myelopathy of 13.8 {+-} 0.6 Gy after a single fraction and 14.9 {+-} 0.9 Gy after two fractions. An increase in the number of fractions to four resulted in an ED{sub 50} of 14.3 {+-} 0.6 Gy. The total physical absorbed dose to the blood in the vasculature of the spinal cord during BNCT using BPA was 80% high-LET radiation. It was observed that fractionation was of minor significance in the amelioration of damage to the normal central nervous system in the rat after boron neutron capture irradiation. 30 refs., 5 figs., 3 tabs.

  6. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    PubMed

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions. PMID:26056878

  7. Single-ion microbeam as a tool for low-dose radiation effects investigations

    NASA Astrophysics Data System (ADS)

    Gerardi, Silvia; Galeazzi, Giuseppe; Cherubini, Roberto

    2006-05-01

    Practical assessment of human radiation exposure risk deserves particular attention especially for low doses (and low dose rates), which concern environmental and occupational exposure. At these dose levels ionizing radiation exposures involve mainly isolated charged particle tracks, which strike individual cells at time intervals averaging from weeks to several years apart. Accelerator-based microbeam irradiation technique offers a unique tool to mimic such an exposure, allowing irradiating single cells individually with micrometer precision and with a preset number of charged particles down to one particle per cell. A horizontal single-ion microbeam facility for single-cell irradiations has been designed and set up at the INFN-LNL 7MV CN Van de Graaff accelerator. The light ion beam is collimated in air down to a section of 2-3µm in diameter by means of appropriate pinholes. Semi-automatic cell visualization and automatic cell positioning and revisiting system, based on an inverted phase contrast optical microscope and on X-Y translation stages with 0.1µm positioning precision, has been developed. An in-house-written software allows to control remotely the irradiation protocol. As a distinctive feature of the facility, cell recognition is performed without using fluorescent staining and UV light. Particle detection in air, behind the biological sample, is based on a silicon detector while in-air beam profile and precise hit position measurements are accomplished by a custom-made cooled-CCD camera and Solid State Nuclear Track detectors, respectively. A particle counting rate of less than 1 ion/sec can be reached.

  8. Single doses of THC and cocaine decrease proficiency of impulse control in heavy cannabis users

    PubMed Central

    van Wel, J H P; Kuypers, K P C; Theunissen, E L; Toennes, S W; Spronk, D B; Verkes, R J; Ramaekers, J G

    2013-01-01

    BACKGROUND AND PURPOSE Cannabis is the most popular drug used in the European Union, closely followed by cocaine. Whereas cannabis impairs neurocognitive function in occasional cannabis users, such impairments appear less prominent in heavy users, possibly as a result of tolerance. The present study was designed to assess whether the impairing effects of Δ9-tetrahydrocannabinol (THC) in heavy cannabis users would present in a wide range of neuropsychological functions or selectively affect specific performance domains. We also assessed the acute effects of cocaine on neurocognitive functions of heavy cannabis users. EXPERIMENTAL APPROACH Heavy cannabis users, who had a history of cocaine use (n = 61), participated in a double-blind, placebo-controlled, three-way crossover study. Subjects received single doses of cocaine HCl (300 mg), cannabis (THC μg·kg−1) and placebo, and completed a number of tests measuring impulse control and psychomotor function. KEY RESULTS Single doses of cannabis impaired psychomotor function and increased response errors during impulsivity tasks. Single doses of cocaine improved psychomotor function and decreased response time in impulsivity tasks, but increased errors. CONCLUSIONS AND IMPLICATIONS Heavy cannabis users display impairments in a broad range of neuropsychological domains during THC intoxication. Impairments observed in psychomotor tasks, but not in impulsivity tasks, appeared smaller in magnitude as compared with those previously reported in occasional cannabis users. Heavy cannabis users were sensitive to the stimulating and inhibitory effects of cocaine on psychomotor function and impulsivity respectively. The reduction in proficiency in impulse control may put drug users at increased risk of repeated drug use and addiction. PMID:24106872

  9. Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

    PubMed

    Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel

    2016-10-01

    Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment. PMID:26856301

  10. Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques.

    PubMed

    Kalaiselvan, R; Mohanta, G P; Madhusudan, S; Manna, P K; Manavalan, R

    2007-08-01

    The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta-cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p < 0.05). The rise in gastric pH (pH > 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH. PMID:17867556

  11. Hemodynamic effects of spinal anesthesia in the elderly: single dose versus titration through a catheter.

    PubMed

    Favarel-Garrigues, J F; Sztark, F; Petitjean, M E; Thicoïpé, M; Lassié, P; Dabadie, P

    1996-02-01

    Sixty elderly patients (> 70 yr old) undergoing surgery for hip fracture were prospectively studied in order to compare hemodynamic tolerance of titrated doses of hyperbaric bupivacaine using continuous spinal anesthesia (CSA) versus single-dose spinal anesthesia (SDSA). Patients were randomized into two groups (CSA group: n = 30; SDSA group: n = 30). The SDSA patients received 10-15 mg of 0.5% hyperbaric bupivacaine (based on age and height), and the CSA patients received a starting dose of 5 mg of 0.5% hyperbaric bupivacaine, followed after 15 min by optional reinjection of 2.5 mg every 5 min until a T10 level sensory block was reached. Onset of anesthesia, noninvasive hemodynamic variables and the need for ephedrine were studied for 4 h after induction of anesthesia. Spinal anesthesia was successful in all patients. Decreases in mean arterial pressure were significantly less frequent and less pronounced in the CSA group (19.9% +/- 1.6% of the baseline value) than in the SDSA group (40.2% +/- 1.9%, P < 0.0001). The mean dose of ephedrine was significantly less in the CSA group (1.8 +/- 0.7 mg, administered to only 37% of patients) than in the SDSA group (19.4 +/- 3.3 mg administered to all patients, P < 0.0001). No late complications related to the spinal anesthesia technique were observed in either group. We concluded that CSA, using small titrated doses of 0.5% hyperbaric bupivacaine, is safe, efficient, and provides better hemodynamic stability than SDSA in elderly patients. PMID:8561333

  12. Single dose of rituximab in children with steroid-dependent minimal change nephrotic syndrome

    PubMed Central

    Niu, Xiao-Ling; Hao, Sheng; Wang, Ping; Zhang, Wei; Guo, Gui-Mei; Wu, Ying; Kuang, Xin-Yu; Zhu, Guang-Hua; Huang, Wen-Yan

    2016-01-01

    Rituximab (RTX) can be used in children with nephrotic syndrome, particularly in those with steroid-dependent nephrotic syndrome (SDNS). However, at present there is no unified standard of how to use RTX, with regard to the amount of doses and frequency, in children with nephrotic syndrome. The study aimed to investigate the therapeutic efficacy of a single dose of RTX in children with steroid-dependent minimal change nephrotic syndrome (SD-MCNS). The patients with biopsy-proven minimal change disease (MCD) and clinical features of SDNS received a single dose of RTX (375 mg/m2). The toxicity and side effects of RTX were also observed. The study included 19 patients (10 males and 9 females). Follow-up of the patients was 1–50 months (28.1±16.6 months). B-cell depletion was achieved with RTX infusion (CD20<0.5%) and lasted 1–6 months (mean, 2.92±1.57 months). During follow-up, 10 patients remained in complete remission and did not relapse without administration of oral steroids or immunosuppressants for 4–50 months (mean, 30.1±12.6 months), despite recovery of the B-cell count. Nine patients relapsed in the process of reducing steroids, thus, treatment was maintained at a lower dosage (T=0, P<0.05) than prior to use of RTX. The number of relapses also decreased significantly (T=95, P<0.05). Five of the patients relapsed after stopping steroid for several months. At the end of follow-up, the efficacy of a single induction of RTX was 47.4% (9/19). There were no significant side effects associated with administration of RTX. In conclusion, RTX is a safe and effective alternative for children with SD-MCNS. RTX is an effective treatment for the rapid induction of remission and reduces relapse and steroid dependency. A single dose of RTX for children with SD-MCNS is recommended for rapid induction of remission, reduction of long-term steroid dosage, and decrease in the number of relapses, as it has few side effects. PMID:27446549

  13. Interstitial pregnancy treated with a single-dose of systemic methotrexate: A successful management

    PubMed Central

    Corioni, Serena; Perelli, Federica; Bianchi, Claudia; Cozzolino, Mauro; Maggio, Luana; Masini, Giulia; Coccia, Maria Elisabetta

    2015-01-01

    Interstitial pregnancy is an ectopic pregnancy at high hemorrhagic risk. It often poses a diagnostic and therapeutic challenge to the clinician, with a significant risk of morbidity and mortality. It presents a difficult management problem with no absolute standard of care; the most appropriate treatment technique for these pregnancies remains controversial. We describe a case of unruptured interstitial pregnancy successfully treated with a single-dose of systemic methotrexate with subsequent ultrasound and serum beta human chorionic gonadotropin monitoring. Medical management can be a safe and successful option in selected cases that satisfy specific criteria and in women who are able to be monitored after treatment. PMID:26109980

  14. [Quantitative EEG analysis of a single dose of psychotropic drugs in healthy probands].

    PubMed

    Fischer, W; Streubel, F R; Heydenreich, F; Rabending, G

    1986-08-01

    In a series of 74 experiments in a double blind study, 25 healthy test persons were medicated with a single dose of Clomipramin, Desipramin, Imipramin, Diazepam, Carbamazepin, Haloperidol, and a placebo. At the end of one hour, and again at the end of three hours, an EEG was made whose frequency analysis revealed significant changes in about half the test persons. The antidepressives induced an increase in the theta waves, the slow alpha waves, and the slow beta waves, and a decrease in the fast alpha waves. The factors influencing the EEG are discussed. PMID:3786575

  15. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals

    PubMed Central

    Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

    2015-01-01

    Introduction Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives Trends in FDA approved FDC in the period 1980–2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. Materials and Methods New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. Results During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. Conclusion FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination. PMID:26469277

  16. Inhibition of cytochrome bc1 as a strategy for single-dose, multi-stage antimalarial therapy.

    PubMed

    Stickles, Allison M; Ting, Li-Min; Morrisey, Joanne M; Li, Yuexin; Mather, Michael W; Meermeier, Erin; Pershing, April M; Forquer, Isaac P; Miley, Galen P; Pou, Sovitj; Winter, Rolf W; Hinrichs, David J; Kelly, Jane X; Kim, Kami; Vaidya, Akhil B; Riscoe, Michael K; Nilsen, Aaron

    2015-06-01

    Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage Plasmodium parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome bc1 (cyt bc1) inhibitors, including the novel 4(1H)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria. Although cyt bc1 inhibitors are generally classified as slow-onset antimalarials, we found that a single dose of ELQ-400 rapidly induced stasis in blood-stage parasites, which was associated with a rapid reduction in parasitemia in vivo. ELQ-400 also exhibited a low propensity for drug resistance and was active against atovaquone-resistant P. falciparum strains with point mutations in cyt bc1. Ultimately, ELQ-400 shows that cyt bc1 inhibitors can function as single-dose, blood-stage antimalarials and is the first compound to provide combined treatment, prophylaxis, and transmission blocking activity for malaria after a single oral administration. This remarkable multi-stage efficacy suggests that metabolic therapies, including cyt bc1 inhibitors, may be valuable additions to the collection of single-dose antimalarials in current development. PMID:25918204

  17. Inhibition of Cytochrome bc1 as a Strategy for Single-Dose, Multi-Stage Antimalarial Therapy

    PubMed Central

    Stickles, Allison M.; Ting, Li-Min; Morrisey, Joanne M.; Li, Yuexin; Mather, Michael W.; Meermeier, Erin; Pershing, April M.; Forquer, Isaac P.; Miley, Galen P.; Pou, Sovitj; Winter, Rolf W.; Hinrichs, David J.; Kelly, Jane X.; Kim, Kami; Vaidya, Akhil B.; Riscoe, Michael K.; Nilsen, Aaron

    2015-01-01

    Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage Plasmodium parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome bc1 (cyt bc1) inhibitors, including the novel 4(1H)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria. Although cyt bc1 inhibitors are generally classified as slow-onset antimalarials, we found that a single dose of ELQ-400 rapidly induced stasis in blood-stage parasites, which was associated with a rapid reduction in parasitemia in vivo. ELQ-400 also exhibited a low propensity for drug resistance and was active against atovaquone-resistant P. falciparum strains with point mutations in cyt bc1. Ultimately, ELQ-400 shows that cyt bc1 inhibitors can function as single-dose, blood-stage antimalarials and is the first compound to provide combined treatment, prophylaxis, and transmission blocking activity for malaria after a single oral administration. This remarkable multi-stage efficacy suggests that metabolic therapies, including cyt bc1 inhibitors, may be valuable additions to the collection of single-dose antimalarials in current development. PMID:25918204

  18. Toxicokinetics of acrylamide in rats and humans following single oral administration of low doses

    SciTech Connect

    Kopp, Eva Katharina; Dekant, Wolfgang

    2009-03-01

    The rodent carcinogen acrylamide (AA) is formed during preparation of starch-containing foods. AA is partly metabolized to the genotoxic epoxide glycidamide (GA). After metabolic processing, the mercapturic acids N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), rac-N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) and rac-N-acetyl-S-(1-carbamoyl-moyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) are excreted with urine. In humans, AAMA can be sulfoxidized to AAMA-sulfoxide. The aim of this study was to assess potential species-differences in AA-toxicokinetics in rats and humans after single oral administration of doses similar to the daily human dietary exposure. Male Fischer 344 rats (n = 5/dose group) were administered 20 and 100 {mu}g/kg b.w. {sup 13}C{sub 3}-AA in deionized water via oral gavage. Human subjects (n = 3/gender) were orally administered 0.5 and 20 {mu}g/kg b.w. {sup 13}C{sub 3}-AA with drinking water. Urine samples were collected in intervals for 96 and 94 h, respectively. Urinary concentrations of {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide were monitored by liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 66.3% and 70.5% of the 20 and 100 {mu}g/kg b.w. doses in rats and for 71.3% and 70.0% of the 0.5 and 20 {mu}g/kg b.w. doses in humans. In rats, {sup 13}C{sub 3}-AAMA accounted for 33.6% and 38.8% of dose and 32.7% and 31.7% of dose was recovered as {sup 13}C{sub 3}-GAMA; {sup 13}C{sub 3}-AAMA-sulfoxide was not detected in rat urine. In humans, {sup 13}C{sub 3}-AAMA, {sup 13}C{sub 3}-GAMA and {sup 13}C{sub 3}-AAMA-sulfoxide accounted for 51.7% and 49.2%, 6.3% and 6.4% and 13.2% and 14.5% of the applied dose, respectively. The obtained results suggest that the extent of AA bioactivation to GA in humans is lower than in rodents.

  19. Total Dose Effects on Single Event Transients in Digital CMOS and Linear Bipolar Circuits

    NASA Technical Reports Server (NTRS)

    Buchner, S.; McMorrow, D.; Sibley, M.; Eaton, P.; Mavis, D.; Dusseau, L.; Roche, N. J-H.; Bernard, M.

    2009-01-01

    This presentation discusses the effects of ionizing radiation on single event transients (SETs) in circuits. The exposure of integrated circuits to ionizing radiation changes electrical parameters. The total ionizing dose effect is observed in both complementary metal-oxide-semiconductor (CMOS) and bipolar circuits. In bipolar circuits, transistors exhibit grain degradation, while in CMOS circuits, transistors exhibit threshold voltage shifts. Changes in electrical parameters can cause changes in single event upset(SEU)/SET rates. Depending on the effect, the rates may increase or decrease. Therefore, measures taken for SEU/SET mitigation might work at the beginning of a mission but not at the end following TID exposure. The effect of TID on SET rates should be considered if SETs cannot be tolerated.

  20. Inhibitory effect of single and repeated doses of nilotinib on the pharmacokinetics of CYP3A substrate midazolam.

    PubMed

    Zhang, Hefei; Sheng, Jennifer; Ko, Jin H; Zheng, Cheng; Zhou, Wei; Priess, Petra; Lin, Wen; Novick, Steven

    2015-04-01

    Effects of single and repeated doses of nilotinib on the pharmacokinetics of midazolam, a cytochrome P450 3A (CYP3A) substrate, were assessed in 2 separate studies. In the single-dose nilotinib study, 18 healthy subjects were randomized to 6 treatment sequences to receive single dose of nilotinib 600 mg, midazolam 4 mg, and coadministration of both in a crossover manner. In the repeated-dose nilotinib study, 19 chronic myeloid leukemia patients took a single dose of midazolam 2 mg on days 1 and 13, and nilotinib 400 mg twice daily from days 2-13. In the single-dose study, the geometric mean ratio of the area under the plasma concentration time curve extrapolated to infinity (AUC(inf)) of midazolam plus nilotinib vs. midazolam was 1.3 (90%CI, 1.2-1.5) and the maximum observed serum concentration (C(max)) was 1.2 (90%CI, 1.0-1.4). In the repeated-dose study, the values for AUC(inf) and C(max) were 2.6 (90%CI, 2.1-3.3) and 2.0 (90%CI, 1.7-2.4), respectively. These results indicate that single-dose and repeated-dose administration of nilotinib results in weak and moderate inhibition of CYP3A, respectively. Therefore, appropriate monitoring and dose adjustment may be needed for drugs that are mainly metabolized by CYP3A, and have narrow therapeutic index, when coadministered with nilotinib. PMID:25418605

  1. Compendium of Single-Event Latchup and Total Ionizing Dose Test Results of Commercial Analog to Digital Converters

    NASA Technical Reports Server (NTRS)

    Irom, Farokh; Agarwal, Shri G.

    2012-01-01

    This paper reports single-event latchup and total dose results for a variety of analog to digital converters targeted for possible use in NASA spacecraft's. The compendium covers devices tested over the last 15 years.

  2. Comparative radiation dose mapping of single fruit type and mixed tropical fruit boxes for export from Hawaii

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quarantine treatment protocols to disinfest fresh agricultural commodities of quarantine pests are traditionally developed for and applied to single commodities. Recently, generic radiation treatments were approved in the USA to control insect pests irrespective of commodity. Approved generic doses ...

  3. Single-Grain Optical Dating Properties of JSC Mars-1: Preliminary Measurements of Radiation Dose Response and Sensitivity Change

    NASA Astrophysics Data System (ADS)

    Lepper, K.

    2003-03-01

    A preliminary evaluation of radiation dose response and measurement induced sensitivity change, two fundamental optical dating properties, of single sand-sized grains extracted from the JSC Mars-1 simulant.

  4. Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

    NASA Astrophysics Data System (ADS)

    Xiao, Yao; Guo, Hong-Xia; Zhang, Feng-Qi; Zhao, Wen; Wang, Yan-Ping; Zhang, Ke-Ying; Ding, Li-Li; Fan, Xue; Luo, Yin-Hong; Wang, Yuan-Ming

    2014-11-01

    Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed.

  5. Amitriptyline pharmacokinetics. Single doses of Lentizol compared with ordinary amitriptyline tablets.

    PubMed

    Burch, J E; Hullin, R P

    1981-01-01

    Two separate single doses of Lentizol (W. R. Warner, Pontypool, U.K.), a sustained-release preparation of amitriptyline (AT) were taken by each of six healthy subjects. Plasma concentrations of AT and of nortriptyline (NT) were determined at intervals over a period of 48 or 72 h. Faeces were collected and their drug content measured. Results were compared with those obtained when the same subjects took ordinary AT tablets. AT was found in the faeces after the ingestion of Lentizol or of ordinary AT tablets. However, after NT tablets negligible amounts of NT appeared in the faeces. AT was sometimes absorbed slowly from Lentizol, but on other occasions it was absorbed as rapidly as from ordinary tablets. Plasma levels of AT 24 h after the dose were usually not higher after Lentizol than after an equal dose of ordinary tablets. The systemic bioavailability of Lentizol as judged by areas under the plasma concentration-time curves, both for AT and for the NT formed metabolically, was on average lower than that of the ordinary tablets. However, the amounts of AT found in the faeces were not large enough to account for the AT area reduction by simple failure of absorption. Possible explanations of the discrepancy are discussed. PMID:6791203

  6. Single dose pharmacokinetics of manidipine in hepatic impaired patients and healthy controls.

    PubMed

    Deroubaix, X; Lins, R L; Lens, S; Allemon, A; Jeanbaptiste, B; Poli, G; Acerbi, D; Stockis, A; Ventura, P

    1998-07-01

    The pharmacokinetics and safety of a single oral dose of 20 mg manidipine dihydrochloride have been studied in 8 patients with mild to moderate hepatic impairment (grade A or B in Child's classification, or score < or = 7 in Pugh's modification of Child's classification), and in 12 healthy subjects. They received one 20 mg manidipine dihydrochloride tablet with 100 ml of tap water after a standard breakfast. Manidipine was determined using HPLC with electrochemical detection from plasma samples taken up to 24 or 36 h after dosing. The medication was well tolerated. A trend toward higher Cmax, AUC, and MRT was observed in patients with a more severe hepatic impairment, as a consequence of reduction in the liver metabolic function. Patients with grade A hepatic impairment did not exhibit significantly altered pharmacokinetics with respect to healthy subjects, while grade B impairment patients had significantly higher AUC and MRT. Tmax values pointed to reduced absorption rate in patients compared to healthy subjects; the changes were more evident in grade B than grade A patients, although statistical significance was not reached. The reduction in absorption rate in grade B patients is probably related to their higher mean age, since this effect has been reported for manidipine. The pharmacokinetics of manidipine seem only modified in patients with a certain degree of hepatic impairment (at least Pugh grade 6 and Child grade B); therefore, adaptation of the dosing regimen does not seem to be generally recommendable, but should be modulated according to the liver status of the patient. PMID:9707354

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

    PubMed

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

    2008-06-01

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

  8. Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise.

    PubMed

    Nakhostin-Roohi, Babak; Niknam, Zahra; Vaezi, Nasrin; Mohammadi, Sadollah; Bohlooli, Shahab

    2013-01-01

    Methylsulfonylmethane (MSM) is a sulfur-containing compound commonly found in diet and known to reduce oxidative stress. This trial was conducted to determine whether single dose supplementation with MSM attenuates post-exercise oxidative stress in healthy untrained young men. Sixteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into 2 groups: Methylsulfonylmethane (MSM) (n = 8) and placebo (n = 8). The participants took supplementation or placebo before running on treadmill for 45 min at 75% VO2max. The MSM supplementation was prepared in water as 100 mg/ kg body weight. The placebo group received water. Serum Malondealdehyde (MDA), uric acid, bilirubin, protein carbonyl (PC) and plasma vitamin E levels were determined as the markers of oxidative stress. Plasma GSH (reduced Glutathione) and total antioxidant capacity (TAC) were measured as markers of plasma antioxidant system. MSM supplementation successfully lowered serum PC 2 and 24 h after exercise. Plasma TAC in MSM group was higher at 24 h after exercise. Serum level of uric acid and bilirubin were significantly low immediately after exercise in MSM supplemented group. There was no significant difference between groups in terms of plasma GSH level. These results complement earlier studies showing anti-oxidant effect of MSM and suggest that single dose oral supplementation with MSM lowers exercise induced oxidative stress in healthy untrained young men, but is not adequate to significantly affect plasma GSH level. PMID:24523764

  9. Enhancement of monoclonal antibody binding to melanoma with single dose radiation or hyperthermia

    SciTech Connect

    Stickney, D.R.; Gridley, D.S.; Kirk, G.A.; Slater, J.M.

    1987-01-01

    We undertook this study to determine whether radiation (10 Gray, single dose) or water bath hyperthermia (41 degrees C, 45 min) could enhance binding of /sup 111/In-labeled anti-p97a monoclonal antibody (MAb) to human melanoma tumors transplanted subcutaneously into nude mice. Sixty animals were given injections of 1-2 X 10(7) Brown C5513 melanoma cells. At 1-2 weeks postinjection, two-thirds of the mice were treated (one-third served as controls). Within 3 hours after treatment, each animal was given iv 2 muCi /sup 111/In-anti-p97a MAb. At 24 and 48 hours thereafter, whole-body scans were done with the use of a MaxiCamera 300 A/M unit, and the ratio of activity at the tumor and liver was determined. Some animals were kept for 7 days posttreatment, whereas others were taken after the 48-hour scan for determination of biodistribution of the radiolabeled complex. Enhancement of MAb binding was demonstrated by either modality, although enhancement was more consistent with radiation. The therapeutic efficacy of MAb may be enhanced with increased binding of radioactive MAb complexes through single dose radiation or hyperthermia.

  10. 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

  11. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    PubMed

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. PMID:27425792

  12. Palonosetron-A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

    SciTech Connect

    Siddiqi, Nasir H.; Khan, Atif J.; Devlin, Phillip M.

    2009-01-15

    Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.

  13. Single-dose metronidazole clears Opalina sp. from juvenile Bufo woodhousii.

    PubMed

    Nickol, Devin R; Tufts, Danielle M

    2013-06-01

    Protozoans of the family Opalinidae are intestinal commensals in amphibians. To test the hypothesis that these organisms are susceptible to the antiprotozoal antibiotic metronidazole, we randomly assigned 60 juvenile Woodhouse's toads ( Bufo woodhousii ) to receive a single oral dose of metronidazole or water. In pilot trials, the prevalence of opalinids in untreated members of this population was over 70%. One-third of the study population was dissected at each of 3 time points: 18 hr, 1 wk, and 2 wk post-treatment. An examiner blinded to the toad's treatment history determined the presence or absence of opalinids using a dissecting microscope. Opalinids were found in 3/10 toads in the treatment group and 9/10 in the control group after 18 hr (P < 0.02), in none of the treatment group and 8/10 in the control group after 1 wk (P < 0.001), and in none of the treatment group and 10/10 in the control group after 2 wk (P < 0.0001). These results suggest that a single-dose of metronidazole quickly and reliably clears opalinids from juvenile Woodhouse's toads with no evidence of short-term recurrence. The treatment was well tolerated, with no apparent morbidity and no mortality in either group. Future exploration of opalinid-related host fitness consequences may be facilitated by this simple method of developing a protozoan-free host population. PMID:23339344

  14. Single-Dose Pharmacokinetics of Different Oral Sodium Nitrite Formulations in Diabetes Patients

    PubMed Central

    Predmore, Benjamin L.; Flanagan, Douglas R.; Giordano, Tony; Qiu, Yang; Brandon, Angela; Lefer, David J.; Patel, Rakesh P.; Kevil, Christopher G.

    2012-01-01

    Abstract Background Diabetic foot ulcers, although associated with macrovascular disease and neuropathy, have a microvascular disease causing ischemia not amenable to surgical intervention. Nitrite selectively releases nitric oxide in ischemic tissues, and diabetes subjects have low nitrite levels that do not increase with exercise. This study explores the safety and pharmacokinetics of a single dose of sodium nitrite in subjects with diabetic foot ulcers. Subjects and Methods Using a blinded, randomized crossover study design, 12 subjects with diabetes mellitus and active or healed foot ulcers received a single dose of sodium nitrite on two occasions 7–28 days apart, once with an immediate release (IR) formulation and once with an enteric-coated (EC) formulation for delayed release. Serum nitrite, nitrate, methemoglobin, sulfhemoglobin, blood pressure, pulse rate, complete blood count, chemistry panel, electrocardiogram, and adverse events were followed for up to 6 h after each dose. The IR and EC nitrite levels were analyzed by one-way analysis of variance and by pharmacokinetic modeling. Results The IR formulation elevated nitrite levels between 0.25 and 0.75 h (P<0.05). The EC formulation did not elevate nitrite levels significantly, but both formulations gave plasma nitrite levels previously suggested to be therapeutic (approximately 2–5 μM). The IR formulation gave an asymptomatic blood pressure drop of 10/6 mm Hg (P<0.003), and two subjects experienced mild flushing. There was no elevation of methemoglobin or other safety concerns. Pharmacokinetic modeling of plama nitrite levels gave r2 values of 0.81 and 0.97 for the fits for IR and EC formulations, respectively. Conclusions Oral sodium nitrite administration is well tolerated in diabetes patients. PMID:22468627

  15. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study

    PubMed Central

    Eissa, Maha M.; El-Moslemany, Riham M.; Ramadan, Alyaa A.; Amer, Eglal I.; El-Azzouni, Mervat Z.; El-Khordagui, Labiba K.

    2015-01-01

    Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting

  16. Single-dose Toxicity of Water-soluble Ginseng Pharmacopuncture Injected Intramuscularly in Rats

    PubMed Central

    Yu, Junsang; Sun, Seungho; Lee, Kwangho; Kwon, Kirok

    2015-01-01

    Objectives: Radix Ginseng has been traditionally used as an adaptogen that acts on the adrenal cortex and stimulates or relaxes the nervous system to restore emotional and physical balance and to improve well-being in cases of degenerative disease and/or old age. Radix Ginseng has been used for a long time, but the safety of ginseng pharmacopuncture needs testing. This study was done to analyze the single-dose toxicity of water-soluble ginseng pharmacopuncture (GP) intramuscular injections in rats. Methods: All experiments were performed at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). Each group contained 10 Sprague-Dawley rats, 5 males and 5 females. GP was prepared in a sterile room at the Korean Pharmacopuncture Institute under regulations of Good Manufacturing Practice (GMP). GP dosages were 0.1, 0.5 and 1.0 mL for the experimental groups; normal saline was administered to the control group. The animals general condition was examined daily for 14 days, and the rats were weighed on the starting day and at 3, 7 and 14 days after administration of the pharmacopuncture. Hematological and biochemistry tests and autopsies were done to test the toxicological effect of GP after 14 days. This study was performed with approval from the Institutional Animal Ethics Committee of Biotextech. Results: No deaths were found in this single-dose toxicity test of intramuscular injections of GP, and no significant changes in the general conditions, body weights, hematological and biochemistry tests, and autopsies were observed. The local injection site showed no changes. Based on these results, the lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results suggest that GP is relatively safe. Further studies, including a repeated toxicity test, are needed to provide more concrete evidence for the safety of GP. PMID:26120491

  17. SU-E-T-568: Neutron Dose Survey of a Compact Single Room Proton Machine

    SciTech Connect

    Chen, Y; Prusator, M; Islam, M; Johnson, D; Ahmad, S

    2015-06-15

    Purpose: To ensure acceptable radiation limits are maintained for those working at and near the machine during its operation, a comprehensive radiation survey was performed prior to the clinical release of Mevion S250 compact proton machine at Stephenson Oklahoma Cancer Center. Methods: The Mevion S250 proton therapy system consists of the following: a superconducting cyclotron to accelerate the proton particles, a passive double scattering system for beam shaping, and paired orthogonal x-ray imaging systems for patient setup and verification via a 6D robotic couch. All equipment is housed within a single vault of compact design. Two beam delivery applicators are available for patient treatment, offering field sizes of as great as 14 cm and 25 cm in diameter, respectively. Typical clinical dose rates are between 1 and 2 Gy/min with a fixed beam energy of 250 MeV. The large applicator (25 cm in diameter) was used in conjunction with a custom cut brass aperture to create a 20 cm x 20 cm field size at beam isocenter. A 30 cm − 30 cm − 35 cm high density plastic phantom was placed in the beam path to mimic the conditions creating patient scatter. Measurements integrated-ambient-neutron-dose-equivalence were made with a SWENDII detector. Gantry angles of 0, 90 and 180 degrees, with a maximum dose rate of 150 MU/min (for large applicator) and beam configuration of option 1 (range 25 cm and 20 cm modulation), were selected as testing conditions. At each point of interest, the highest reading was recorded at 30 cm from the barrier surface. Results: The highest neutron dose was estimated to be 0.085 mSv/year at the console area. Conclusion: All controlled areas are under 5 mSv/year and the uncontrolled areas are under 1 mSv/year. The radiation protection provided by the proton vault is of sufficient quality.

  18. Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

    SciTech Connect

    Amini, Arya; Westerly, David C.; Waxweiler, Timothy V.; Ryan, Nicole; Raben, David

    2015-10-01

    Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involved lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V{sub 70} (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V{sub 70} was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.

  19. Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

    SciTech Connect

    Greco, Carlo; Zelefsky, Michael J.; Lovelock, Michael; Fuks, Zvi; Hunt, Margie; Rosenzweig, Kenneth; Zatcky, Joan; Kim, Balem; Yamada, Yoshiya

    2011-03-15

    Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses ({<=}22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

  20. QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

    PubMed

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. PMID:26812258

  1. Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide.

    PubMed

    Berger, William E; Gillen, Michael; Eckerwall, Göran; Uryniak, Tom; Trudo, Frank J; Lampl, Kathy L

    2014-01-01

    Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov. PMID:24717790

  2. Efficacy of albendazole, levamisole and ivermectin against gastro-intestinal nematodes in naturally infected goats at the National Semi-arid Resources Research Institute, Serere, Uganda.

    PubMed

    Byaruhanga, C; Okwee-Acai, J

    2013-07-01

    A study was conducted between April and July, 2011 to determine and compare the efficacy of albendazole (ABZ), levamisole (LVM) and ivermectin (IVM) against gastrointestinal nematodes in naturally infected Mubende and Boer crossbred goats at the National Semi-arid Resources Research Institute in Serere, Uganda. Forty Mubende goats and 31 Boer crosses were each blocked by age and sex and randomly assigned to four groups. The first group of each breed served as the untreated control, the second was treated with albendazole (5mg/kg BW), the third with levamisole hydrochloride and oxyclozanide (7.5 and 15 mg/kg BW) and the fourth with ivermectin (0.2mg/kg BW). Each group included 7-11 animals. Treatments were administered with doses of goats in albendazole and ivermectin, and doses of sheep in levamisole, as recommended by the manufacturers. In the treated groups, goats received anthelmintics basing on individual weights. Fecal egg counts, expressed as eggs per gram and larval cultures were done on day zero before treatment and on day 13 after anthelmintic treatment. Efficacy for each anthelmintic was determined by the Fecal Egg Count Reduction Test (FECRT). In Mubende goats, ABZ, LVM, and IVM reduced FEC by 28.5%, 91%, and 98%, respectively. In Boer crosses, ABZ, LVM, and IVM reduced FEC by 11%, 84.88% and 78.47%, respectively. At a 95% CI, only IVM was more effective in Mubende goats than Boer crosses (t=2.564, p<0.05). This may indicate occurrence of anthelmintic resistance in the goat farming sector in Uganda. Further studies need to be done to clarify the state of efficacy of the commonly used anthelmintics covering different agro ecological zones and species of animals in Uganda. PMID:23394798

  3. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate-release/extended release

    PubMed Central

    Devarakonda, Krishna; Kostenbader, Kenneth; Giuliani, Michael J; Young, Jim L

    2015-01-01

    Objective This study aimed to compare the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) and IR HB/APAP. Setting The study was conducted in a contract research center. Participants The study included healthy adults. Interventions In a three-way crossover study, Study 1, participants received the following treatments: (A1) a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h); (B1) a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1) a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6), followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2) an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2) three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures PK values were compared, and adverse events were assessed. Results Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax) at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%). Steady state was achieved in 2−3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median time to Cmax was longer for IR/ER HB/APAP versus IR HB/APAP (P,0.05). Adverse events were similar across treatments. Conclusion PK outcomes and tolerability were similar for IR/ER HB/APAP and IR HB/APAP. PMID:26392786

  4. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep.

    PubMed

    Lifschitz, A; Virkel, G; Mastromarino, M; Lanusse, C

    1997-04-01

    The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract. PMID:9090047

  5. Synthetic CT: Simulating low dose single and dual energy protocols from a dual energy scan

    SciTech Connect

    Wang, Adam S.; Pelc, Norbert J.

    2011-10-15

    Purpose: The choice of CT protocol can greatly impact patient dose and image quality. Since acquiring multiple scans at different techniques on a given patient is undesirable, the ability to predict image quality changes starting from a high quality exam can be quite useful. While existing methods allow one to generate simulated images of lower exposure (mAs) from an acquired CT exam, the authors present and validate a new method called synthetic CT that can generate realistic images of a patient at arbitrary low dose protocols (kVp, mAs, and filtration) for both single and dual energy scans. Methods: The synthetic CT algorithm is derived by carefully ensuring that the expected signal and noise are accurate for the simulated protocol. The method relies on the observation that the material decomposition from a dual energy CT scan allows the transmission of an arbitrary spectrum to be predicted. It requires an initial dual energy scan of the patient to either synthesize raw projections of a single energy scan or synthesize the material decompositions of a dual energy scan. The initial dual energy scan contributes inherent noise to the synthesized projections that must be accounted for before adding more noise to simulate low dose protocols. Therefore, synthetic CT is subject to the constraint that the synthesized data have noise greater than the inherent noise. The authors experimentally validated the synthetic CT algorithm across a range of protocols using a dual energy scan of an acrylic phantom with solutions of different iodine concentrations. An initial 80/140 kVp dual energy scan of the phantom provided the material decomposition necessary to synthesize images at 100 kVp and at 120 kVp, across a range of mAs values. They compared these synthesized single energy scans of the phantom to actual scans at the same protocols. Furthermore, material decompositions of a 100/120 kVp dual energy scan are synthesized by adding correlated noise to the initial material

  6. Attempt at using the single-aliquot regenerative-dose procedure for the determination of equivalent doses of Upper Palaeolithic burnt stones

    NASA Astrophysics Data System (ADS)

    Tribolo, Chantal; Mercier, Norbert; Valladas, Hélène

    2003-05-01

    The equivalent dose of Upper Palaeolithic quartzite pebbles burnt in prehistoric hearths was determined using the optically stimulated luminescence (OSL) signal and the single-aliquot regenerative-dose (SAR) procedure. Since previously published thermoluminescence (TL) dates for these samples were in agreement with the archaeological record and other chronological data, the TL equivalent doses were used as a reference. The observed discrepancies between some TL and OSL SAR equivalent doses are probably due to accidental bleaching before the stones reached the laboratory, instead of reflecting a deficiency of the SAR procedure. This hypothesis is confirmed by experiments which indicate that bleaching could reach considerable depths in quartzite specimens and significantly deplete the OSL signal.

  7. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults

    PubMed Central

    Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain

  8. Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery

    PubMed Central

    Pan, Jianmin; Yusuf, Mehran B; Dragun, Anthony; Dunlap, Neal; Guan, Timothy; Boling, Warren; Rai, Shesh; Woo, Shiao

    2016-01-01

    Background: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). Methods: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. Results: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 – 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. Conclusions: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control. PMID:27284495

  9. Patient Radiation Dose in Diagnostic and Interventional Procedures for Intracranial Aneurysms: Experience at a Single Center

    PubMed Central

    Chun, Chang Woo; Lee, Cheol Hyoun; Ihn, Yon Kwon; Shin, Yong-Sam

    2014-01-01

    Objective To assess patient radiation doses during cerebral angiography and embolization of intracranial aneurysms in a large sample size from a single center. Materials and Methods We studied a sample of 439 diagnostic and 149 therapeutic procedures for intracranial aneurysms in 480 patients (331 females, 149 males; median age, 57 years; range, 21-88 years), which were performed in 2012 with a biplane unit. Parameters including fluoroscopic time, dose-area product (DAP), and total angiographic image frames were obtained and analyzed. Results Mean fluoroscopic time, total mean DAP, and total image frames were 12.6 minutes, 136.6 ± 44.8 Gy-cm2, and 251 ± 49 frames for diagnostic procedures, 52.9 minutes, 226.0 ± 129.2 Gy-cm2, and 241 frames for therapeutic procedures, and 52.2 minutes, 334.5 ± 184.6 Gy-cm2, and 408 frames for when both procedures were performed during the same session. The third quartiles for diagnostic reference levels (DRLs) were 14.0, 61.1, and 66.1 minutes for fluoroscopy time, 154.2, 272.8, and 393.8 Gy-cm2 for DAP, and 272, 276, and 535 for numbers of image frames in diagnostic, therapeutic, and both procedures in the same session, respectively. The proportions of fluoroscopy in DAP for the procedures were 11.4%, 50.5%, and 36.1%, respectively, for the three groups. The mean DAP for each 3-dimensional rotational angiographic acquisition was 19.2 ± 3.2 Gy-cm2. On average, rotational angiography was used 1.4 ± 0.6 times/session (range, 1-4; n = 580). Conclusion Radiation dose in our study as measured by DAP, fluoroscopy time and image frames did not differ significantly from other reported DRL studies for cerebral angiography, and DAP was lower with fewer angiographic image frames for embolization. A national registry of radiation-dose data is a necessary next step to refine the dose reference level. PMID:25469098

  10. Dose-to-dose variations with single packages of counterfeit medicines and adulterated dietary supplements as a potential source of false negatives and inaccurate health risk assessments.

    PubMed

    Venhuis, B J; Zwaagstra, M E; Keizers, P H J; de Kaste, D

    2014-02-01

    In this report, we show three examples of how the variability in dose units in single packages of counterfeit medicines and adulterated dietary supplements may contribute to a false negative screening result and inaccurate health risk assessments. We describe a counterfeit Viagra 100mg blister pack and a box of an instant coffee both containing dose units with and without an active pharmaceutical ingredient (API). We also describe a purportedly herbal slimming product with capsules that mutually differed in API and impurities. The adulterated dietary supplements contained sibutramine, benzyl-sibutramine, N-desmethyl-sibutramine (DMS), N,N-didesmethyl-sibutramine (DDMS) and several other related impurities. Counterfeit medicines and adulterated dietary supplements are a health risk because their quality is unreliable. Health risks are even greater when such unreliability extends to fundamental differences between dose units in one package. Because dose-to-dose variability for these products is unpredictable, the confidence interval of a sample size is unknown. Consequently, the analyses of a selection of dose units may not be representative for the package. In the worst case, counterfeit or unauthorised medicines are not recognised as such or a health risk is not identified. In order to reduce erroneous results particular care should be taken when analysing a composite of dose units, when finding no API in a dietary supplement and when finding conformity in a suspect counterfeit medicine. PMID:24291553

  11. Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose

    PubMed Central

    Marciani, L; Garsed, K C; Hoad, C L; Fields, A; Fordham, I; Pritchard, S E; Placidi, E; Murray, K; Chaddock, G; Costigan, C; Lam, C; Jalanka-Tuovinen, J; De Vos, W M; Gowland, P A; Spiller, R C

    2014-01-01

    Background Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing. Methods Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. Key Results Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). Conclusions & Inferences Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies. PMID:25060551

  12. Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: randomised trial

    PubMed Central

    Sundar, Shyam; Agrawal, G; Rai, Madhukar; Makharia, M K; Murray, Henry W

    2001-01-01

    Objective To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar). Design Randomised, open label study. Setting Inpatient unit for leishmaniasis in Bihar, India. Participants 91 adults and children with splenic aspirate positive for infection. Interventions Total dose of 5 mg/kg of liposomal amphotericin B given as a single infusion (n=46) or as once daily infusions of 1 mg/kg for five days (n=45). Main outcome measures Clinical and parasitological cure assessed 14 days after treatment and long term definitive cure (healthy, no relapse) at six months. Results All but one person in each group had an initial apparent cure. During six months of follow up, three patients in the single dose group and two in the five dose group relapsed. Complete response (definitive cure) was therefore achieved in 84 of 91 subjects (92%): 42 of 46 patients in the single dose group (91%, 95% confidence interval 79% to 98%) and 42 of 45 in the five dose group (93%, 82% to 99%). Response rates in the two groups were not significantly different. Conclusion Low dose liposomal amphotericin B (5 mg/kg), given either as a five day course or as a single infusion, seems to be effective for visceral leishmaniasis and warrants further testing. What is already known on this topicPentavalent antimony is now ineffective against visceral leishmaniasis in IndiaLiposomal amphotericin B is effective but high cost prohibits its use in developing countriesWhat this study addsLiposomal amphotericin B (5 mg/kg), given as a single infusion or five daily infusions of 1 mg/kg, cured 92% of patientsIf proved effective in larger trials, low dose regimens could make the drug more affordable PMID:11520836

  13. Preparation and characterization of albendazole beta-cyclodextrin complexes.

    PubMed

    Castillo, J A; Palomo-Canales, J; Garcia, J J; Lastres, J L; Bolas, F; Torrado, J J

    1999-12-01

    Albendazole (ABZ), mebendazole (MBZ), and ricobendazole (RBZ) are low-soluble anthelmintic benzimidazole carbamate drugs. To increase their aqueous solubility, three different types of beta-cyclodextrins (CyDs): beta-cyclodextrin (CD), hydroxypropyl-beta-cyclodextrin (HPCD), and methyl-beta-cyclodextrin (MCD) were used. Solubility depended on the type of CyDs. Increased solubility was obtained when the more substituted CyDs (HPCD or MCD) were used instead of nonsubstituted CD. Stability constants were calculated assuming a 1:1 stoichiometry. Calculated stability constant values depended on initial solubility of drug and pH of the medium. Solid ABZ complexes were prepared by coprecipitation and freeze-drying methods. These products were compared with physical mixtures of ABZ and CyDs. The characterization of these products was made by differential scanning calorimetry (DSC) and drug release studies. True inclusion complexes were obtained only by the freeze-drying method. Drug release studies showed that the freeze-dried inclusion complexes increased the solubility rate of ABZ, although a supersaturation effect was observed when drug release studies were performed in nonsink conditions. A bioavailability study on mice was done with a formulation of ABZ:HPCD complex and was compared to a conventional ABZ suspension. A significantly (p < .05) shorter Tmax of absorption was obtained by using the complex formulation. Greater and significant (p < .05) differences for AUC and Cmax were observed. PMID:10612019

  14. Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

    PubMed Central

    2012-01-01

    Background The first meningococcal serogroup C (MenC) conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed. PMID:22316426

  15. Tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel.

    PubMed

    Vaidya, Gaurang Nandkishor; Acevedo, Russell

    2015-02-01

    Tumor lysis syndrome (TLS) is an oncologic emergency characterized by spillage of intracellular material into the blood caused by disruption of massive load of tumor cells. It is more commonly reported in hematological cancers and can have fatal consequences due to renal and multi-organ failure and arrhythmias due to electrolyte imbalance. We describe a case with metastatic breast cancer who presented with TLS after a single dose of paclitaxel, second such case in literature. The development of a risk stratification score to assess the need for hospitalization or close observation of these patients and the documentation of appropriate preventive strategies could help prevent such fatal occurrences. TLS should be included in the differential when cancer patients on treatment present with acute decompensation. PMID:25178848

  16. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

    PubMed

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

    2016-02-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings. PMID:26683233

  17. Flunarizine-pizotifen single-dose double-blind cross-over trial in migraine prophylaxis.

    PubMed

    Cerbo, R; Casacchia, M; Formisano, R; Feliciani, M; Cusimano, G; Buzzi, M G; Agnoli, A

    1986-03-01

    The results of a double-blind cross-over clinical trial involving 27 patients with classical or common migraine are described to compare the prophylactic effect of the calcium entry blocker flunarizine with that of pizotifen. Duration of the treatment was two months, with an evening single-dose administration of both drugs. For most parameters, there was no definite difference between flunarizine and pizotifen in migraine prophylaxis. It has been demonstrated previously that pizotifen is an effective drug in migraine prophylaxis, and these results suggest that flunarizine is effective, too. Weight gain as a side effect was less frequent and less severe with flunarizine than with pizotifen; other side effects showed the same incidence with both drugs. PMID:3516406

  18. Single doses of local betamethasone do not suppress allergic patch test reactions to nickel sulfate.

    PubMed

    Molander, Gerd; Petman, Leena; Kannas, Liisa; Lauerma, Antti I

    2004-04-01

    Topical corticosteroids are usually banned on test areas prior to patch testing. The previous literature on the effect of topical corticosteroids is conflicting. Patients allergic to nickel sulfate were patch tested on 4 sites with nickel on day (D) 0. Intracutaneous betamethasone was injected to test sites on D-1, D0 and D1. NaCl injection on D-1 was control. The patch test reactions were evaluated clinically and with laser Doppler. There were no differences in patch test reaction intensities on sites treated with intracutaneous betamethasone as compared to control. A single local dose of potent corticosteroid does not suppress allergic patch reactions to nickel. The current practice of avoiding topical corticosteroid use prior to patch testing should be re-evaluated. PMID:15186376

  19. Population pharmacokinetics of single-dose riociguat in patients with renal or hepatic impairment

    PubMed Central

    2016-01-01

    Abstract This population pharmacokinetics (PK) analysis characterized the PK of the oral soluble guanylate cyclase stimulator riociguat in patients with renal or hepatic impairment and determined whether smoking affects riociguat dosing. Two phase 1 studies were performed in patients with renal impairment (n = 72, of whom 11 were smokers), and two were performed in those with hepatic impairment (n = 64, of whom 12 were smokers). Plasma and urine samples were collected after a single oral dose of riociguat 1.0 or 0.5 mg. Nonlinear mixed-effects modeling was used to develop a combined, two-compartment population PK model for riociguat and its main metabolite, M1. Riociguat and M1 clearance was split into renal and nonrenal parts; the nonrenal part for riociguat was divided into metabolism to M1 and a metabolic (nonrenal) part. Total clearance of riociguat was 1.912 L/h. The main route of riociguat clearance is metabolism to M1 (1.2 L/h). In this model, hepatic function biomarkers or Child-Pugh classification had no significant effect on riociguat or M1 clearance. Nonrenal (nonmetabolism) riociguat clearance was similar in all groups. Renal clearance (0.242 L/h) contributed less to riociguat total clearance, mainly determined by glomerular filtration (0.174 L/h). Renal impairment reduced riociguat and M1 clearance. Hepatic or renal impairment had limited effects on total exposure to riociguat. However, individual dose adjustment of riociguat should be administered with particular care in patients with moderate hepatic or renal impairment. Riociguat is not recommended in severe hepatic or renal impairment. Smoking reduced riociguat exposure by significantly increasing metabolism to M1. PMID:27162631

  20. Clinical trial with Secnidazole in a single dose in Venezuelan children infected by Giardia intestinalis.

    PubMed

    Di Prisco, M C; Jiménez, J C; Rodríguez, N; Costa, V; Villamizar, J; Silvera, A; Carrillo, M; Lira, C; Zerpa, E; López, Y

    2000-09-01

    The aim of this work was to evaluate in an open, noncomparative study the use of secnidazole in oral suspension given to Venezuelan children infected with Giardia intestinalis, from a community in Carapita, a slum area in Caracas. Seventy children from 2 to 11 years old (38 males and 32 females) were treated with a single oral dose of secnidazole (30 mg/Kg of body weight), after clinical and parasitological evaluation to make the diagnosis of active giardiasis. The effectiveness of treatment was determined by clinical examination and parasitological evaluation of feces samples 15 days after treatment. The results showed 95% of clinical cure with a significant decrease of the frequency of gastrointestinal symptoms. The parasitological cure was 98%, there were 4 failures at the end of treatment. Side effects observed after treatment were of mild intensity, lasting only few hours. These results show that a simple dose of secnidazole in an oral suspension is an effective, safe and well tolerated treatment for giardiasis in children and that this drug may be used as a mass treatment in risk populations. PMID:11029834

  1. Dynamics of the general factor of personality in response to a single dose of caffeine.

    PubMed

    Caselles, Antonio; Micó, Joan C; Amigó, Salvador

    2011-11-01

    General Factor of Personality (GFP) research is an emergent field in personality research. This paper uses a theoretical mathematical model to predict the short-term effects of a dose of a stimulant drug on GFP and reports the results of an experiment showing how caffeine achieves this. This study considers the General Factor of Personality Questionnaire (GFPQ) a good psychometric approach to assess GFP. The GFP dynamic mechanism of change is based on the Unique Trait Personality Theory (UTPT). This theory proposes the existence of GFP which occupies the apex of the hierarchy of personality, and extends from an impulsiveness-and-aggressiveness pole (approach tendency) to an anxiety-and-introversion pole (avoidance tendency). An experiment with 25 volunteers was performed. All the participants completed the GFPQ and the Sensation-Seeking Scale list of adjectives from the trait version of MAACL-R (Multiple Affect Adjective Checklist Revised) on an empty stomach. The participants in the experimental group (20) received 330 mg of caffeine. All the participants filled in a state version form with the sensation-seeking adjectives every 4.5 minutes. This study considers that the Sensation-Seeking Scale list of adjectives from the MAACL-R, available in both trait and state versions, is a good psychometric approach to assess GFP. The results show that GFP is modified by a single dose of caffeine in the direction predicted by the UTPT. PMID:22059314

  2. Single-dose oral toxicity of fermented rice extracts (FREs): a 14-day observation.

    PubMed

    Choi, Jae-Suk; Kim, Joo-Wan; Kim, Ki-Young; Ku, Sae-Kwang; Sohn, Jae Hak

    2014-01-01

    The aim of present research was to determine the acute oral toxicity of fermented rice extracts (FREs), in female and male ICR mice. To investigate the toxicity and identify target organs, FREs were orally administered once to male and female ICR mice at doses of 0 (vehicle control), 500, 1000, or 2000 mg/kg body weight (BW). Effects on mortality, BW, and clinical signs were monitored over 14 days, including changes in the weights and histopathological characteristics of 14 organs, as described in the Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). No treatment-related mortality was observed during the 14-day observation period in either gender. In addition, no FRE-related change was observed in BW or organ weight (OW), clinical indicators, or histopathological findings in this study. Our results suggest that the FRE is non-toxic in mice and is therefore likely to be safe for clinical use. The approximate LD and LD50 in mice after single oral dose of FRE are greater than 2000 mg/kg in female and male ICR mice. Additionally, no specific target organ or negative clinical indicator was detected in this study. PMID:24374435

  3. Studies on a single-dose capsule preparation of poliomyelitis vaccine*

    PubMed Central

    Barnes, Joan M.; Galbraith, N. S.

    1966-01-01

    In view of certain difficulties involved in the administration of poliomyelitis vaccine in liquid form on sugar or in syrup in mass campaigns, trials have been conducted with a new single-dose preparation of live attenuated poliovaccine (Sabin strain) in an emulsion in a gelatin capsule. Each capsule contained a standard dose of vaccine which was shown to be stable in this form. It has been demonstrated that the capsule vaccine was as effective as liquid vaccine both in children and in adults. The capsules were acceptable to adults and children over the age of 5 years, but between 6% and 7% of 4-5-year-old children refused the vaccine in this form owing to difficulty in swallowing the capsules. The authors consider that the capsule may be recommended for the routine immunization of older children and adults and for mass vaccination campaigns. It is suggested that the vaccine could be administered to young children and babies in the course of such campaigns by opening the capsule and mixing the contents with water or sweetened liquid in a spoon. PMID:5296232

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    1997-03-01

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

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

    PubMed Central

    Bernareggi, A; Danese, A; Cavenaghi, L

    1988-01-01

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

  7. Single exposure simultaneous acquisition of digital and conventional radiographs utilizing unaltered dose.

    PubMed

    Oestmann, J W; Greene, R

    1988-11-01

    We describe the simultaneous acquisition of digital and conventional radiographs with a single standard radiographic exposure. A digitizable storage phosphor (ST Imaging Plate, FujiTM) is sandwiched into a radiographic cassette (X-Omatic, KodakTM) behind a conventional radiographic film-screen combination (Lanex medium screens, OC film, KodakTM). The barium fluorohalide storage phosphor is digitized with a helium-neon laser scanner (TCR 201, ToshibaTM), and the conventional radiograph is processed in the standard fashion (M7B, KodakTM). The storage phosphor is exposed by the "wasted" radiation normally exiting the back of the film-screen combination (32% of the cassette entrance dose at 141 kVp). At a standard exposure (6.3 mAs), the conventional radiograph is of unaltered quality, and the digital image appears to have an adequate signal-to-noise ratio for chest studies despite the lower exposure dose. This technique produces twin images of identical spatial and temporal registration and avoids the added radiation exposure normally required to carry out comparative studies. PMID:3234405

  8. [COMPARATIVE STUDY OF ALBENDAZOLE VERSUS NITROFURANS AND NITROIMIDAZOLES IN THE TREATMENT OF GIARDIASIS IN CHILDREN

    PubMed

    Chan Del Pino, Manuel; Cueva Cornejo, Lina; Troyes Rivera, Lucinda

    1999-01-01

    A prospective, longitudinal, comparative, open and aleatory study in Jaen (Cajamarca--Peru), was performed during November 1997 and January of 1998. The objective was to demonstrate the efficacy and tolerance of Albendazol compared with Metronidazol, Furazolidona, Tinidazol and Secnidazol in the treatment of giardiasis in children. 79 children with giardiasis, confirmed by parasitologic studies were evaluated and distributed randorrily for aleatory code in A,B,C,D and E groups. The A group received Albendazol (5 days), the B group Metronidazol (10 days), the C group Furazolidona (10 days), the D group Tinidazol (1 d a) and the E group Secnidazol (1 d a); Clinical controls and coproparasitologic studies were performad during and after the treatment. The cl nical efficacy in the groups was of 100% and the efficacy coproparas tological of 94.1% with Albendazol, 93.3% with Secnidazol and 100% with Metronidazol. Furazolidona and Tinidazol. The global efficacy was excel lent with Al bendazol in 64,7% and in less than 40% with the other drugs, being the biggest pharmacological tolerance with Albendazol (82,3%) and Secnidazol (80%). We conclude that Albendazol is as effective as Metronidazol, Furazolidona, Tinidazol and Secnidazol but faster in eradicating the Giardia lambila in children and with better tolerance that Metronidazol, Furazolidona and Tinidazol. We consider necessary to control Epidemiological factor associated, to eradicate the parasite permanently. PMID:12196811

  9. Evaluation of potential embryo toxicity of albendazole sulphoxide in CF1 mice.

    PubMed

    Teruel, Miriam; Dercole, Jaqueline; Catalano, Rodolfo

    2011-04-01

    Benzimidazole compounds are used in both humans and animals for controlling helminth parasites. Albendazole has teratogenic effects attributed to its active metabolite albendazole sulphoxide. The aim of this work was to evaluate the effect of the latter compound when administered to pregnant CF1 mice during the preimplantation period. Females were superovulated by intraperitoneal injection of 10 IU of eCG and 10 IU of hCG (48h later) and were paired with males of proven fertility. Albendazole sulphoxide (200 mg/kg) was orally administered by gavages at day 1, 2 or 3 of pregnancy; the control group received only the vehicle (carboxymethylcellulose). Females were killed by cervical dislocation at day 4 of pregnancy and embryos were flushed from uteri with Ham F10 media supplemented with bovine serum albumin (0.4%). Number of collected embryos per female, percentage of morphologically normal embryos, differentiation rate and number of cells per embryos were recorded. The variables were analyzed on a per litter basis by Kruskal-Wallis test. There was no effect of albendazole sulphoxide on parameters evaluated (P>0.05). We conclude that the preimplantation mouse embryo development was not significantly affected by albendazole sulphoxide. PMID:21667669

  10. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    PubMed

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. PMID:26150070

  11. Single dose pharmacokinetics of atorvastatin oral formulations using a simple HPLC-UV method.

    PubMed

    Sohail, Muhammad; Ahmad, Mahmood; Minhas, Muhammad Usman

    2016-07-01

    The study was aimed to assess pharmacokinetics of atorvastatin (40 mg) in healthy fasted human subjects by a simple and inexpensive high performance liquid chromatography. Experimental design of the study was a randomized, two way, two periods, crossover study (single dose in fasted conditions). Eighteen (18) healthy male volunteers were enrolled according to FDA guidelines. The plasma samples were assayed using an isocratic High Performance Liquid Chromatography (HPLC) system of Agilent technologies USA consisted of an isocratic pump with column of Thermo Electron Corporation USA (ODS hypersil C(18) 4.6 mm x 250 mm), a UV-visible detector set at λ(max) 237 nm. Maximum plasma concentrations (C(max)) of atorvastatin (Mean ± SEM) for the reference product (A) found to be 13.739±0.210ng/ml & 13.374±0.145ng/ml for test product (B). T(max) values (Mean±SEM) of atorvastatin were 1.222 ±0.060 hours and 1.167±0.057 hours for reference and test products, respectively. The values of AUC(0-oo) (Mean ± SEM) for the reference (A) and test product (B) were 73.955 ± 1.715ng.h/ml and 77.773 ± 1.858ng. h/ml, respectively. Other pharmacokinetic parameters of both products were also determined. A statistical non-significant difference between pharmacokinetic parameters has been found and both brands of atorvastatin showed the same rate and extent of absorption in healthy fasted human volunteers after single dose. A simple and cost effective HPLC method was developed and applied. PMID:27393428

  12. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    SciTech Connect

    Zelefsky, Michael J.; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  13. [Single-dose palliative radiotherapy in inoperable non-small-cell lung carcinoma].

    PubMed

    Scolaro, T; Bacigalupo, A; Giudici, S; Guenzi, M; Vitale, V

    1995-12-01

    The treatment of choice for advanced inoperable non-small cell lung cancer (NSCLC) is radiation therapy. Palliative radiotherapy schedules vary considerably in different centers, but a 30-Gy dose given in ten fractions over two weeks is a typical standard schedule. Our study was aimed at investigating whether a shorter course of only one 10-Gy fraction allows good palliation in the treatment of inoperable NSCLC patients whose main symptoms are related to an intrathoracic lesion. Patients of both sexes and any age, untreated with radiotherapy, with inoperable and histologically or cytologically proved NSCLC were examined. Seventeen patients, too advanced for radical "curative" radiotherapy and whose main symptoms were related to primary intrathoracic lesions, entered the study even though they had metastases. On admission, 76% (13/17) of patients had cough 76% (13/17) dyspnea, 70.7% (12/17) chest pain and 23.6% (4/17) hemoptysis. They received a single dose of 10 Gy, delivered with an 18-Mv linear accelerator via anteroposteriorly opposing portals without spinal cord shielding. Treatment volume usually included the macroscopically detected lesion identified with a CT simulator. Palliation of symptoms was achieved in high rates of patients: 46% for cough, 69% for dyspnea, 83% for pain and 75% for hemoptysis. These results were obtained within one month of treatment. Unfortunately, palliation of symptoms did not last long, decreasing to 42% within two months of the end of treatment and to 32% at three months. Four patients were retreated, one patient three months and three patients two months after the end of radiotherapy. Ten Gy to the target volume were administered as retreatment with spinal cord shielding. Side-effects were mild: nausea in 3 patients (17%), vomiting in one patient (5%) and grade-II dysphagia in two patients were observed and classified according to WHO criteria. Pain increased 24 hours after radiotherapy in five patients. We can conclude that

  14. Bioequivalence study of two imatinib formulations after single-dose administration in healthy Korean male volunteers.

    PubMed

    Jung, J A; Kim, N; Yang, J-S; Kim, T-e; Kim, J-R; Song, G-S; Kim, H; Ko, J W; Huh, W

    2014-12-01

    Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 μg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 μg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · μg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated. PMID:24549963

  15. Single high dose gentamicin for perioperative prophylaxis in orthopedic surgery: Evaluation of nephrotoxicity

    PubMed Central

    Dubrovskaya, Yanina; Tejada, Rainer; Bosco, Joseph; Stachel, Anna; Chen, Donald; Feng, Melinda; Rosenberg, Andrew; Phillips, Michael

    2015-01-01

    Background: Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity. Methods: Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria. Results: Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705), patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07). Conclusion: In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single

  16. Protocol versus Nonprotocol Dosing of Vancomycin in Neonates: A Single Center Evaluation of Steady State Trough Levels.

    PubMed

    Schwartz, Megan L; Wrobel, Joanna; Huntley, Jamalee; Zeilmann, Carla

    2016-06-01

    Objective This study aims to assess the need for modification of the current vancomycin dosing protocol at a single institution by conducting a comparison of dosing per protocol versus off protocol and the resulting first troughs in neonates. Secondary outcomes include comparison of time to first therapeutic steady-state trough, dose at first therapeutic steady-state trough, and success of the consult-to-pharmacy service. Study Design This single center retrospective chart review analyzed patients at a level-IIIb neonatal intensive care unit who received vancomycin and had at least one appropriately drawn trough level documented from 2013 to 2014. Effectiveness of each dosing strategy was evaluated by assessing troughs. Results Approximately 30% of first vancomycin trough levels obtained are within the desired range of 15 to 20 µg/mL and patients achieve therapeutic steady-state trough levels after 3.6 days, regardless of the initial dosing strategy. The current protocol reflects the therapeutic steady state dosing only 22% of the time. The vancomycin consult-to-pharmacy service improves the achievement of goal trough ranges. Conclusion An assessment of doses that achieved a goal vancomycin trough of 15 to 20 µg/mL revealed that a dose of 12.5 mg/kg at the same intervals and age ranges specified in the current protocol would enable the achievement of this higher goal trough. PMID:26862722

  17. Immunogenicity of single-dose diphtheria vaccines based on PLA/PLGA microspheres in guinea pigs.

    PubMed

    Johansen, P; Moon, L; Tamber, H; Merkle, H P; Gander, B; Sesardic, D

    1999-09-01

    Biodegradable polyester microspheres (MS) have shown potential for single-dose vaccines. This study examined the immunogenicity of diphtheria toxoid (Dtxd) microencapsulated in different types of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) MS prepared by the methods of spray-drying and coacervation. We investigated the influence of polymer type (PLGA 50:50 of low M(w); PLA of high M(w); end-group stearylated PLAs of low M(w)) and co-encapsulated excipients (BSA and/or trehalose) on Dtxd content, in vitro release and immunogenicity in guinea pigs. The co-encapsulated trehalose lowered the Dtxd entrapment efficiency in the spray-dried particles from 75 to 56%, whereas albumin alone had no effect in the spray-drying, but improved the encapsulation in the coacervation process. With the hydrophobic, end-group stearylated PLAs, Dtxd could only be encapsulated in the presence of albumin. Guinea pigs immunised with Dtxd-MS made with the relatively hydrophilic PLGA 50:50 exhibited specific and sustained antibody responses over 40 weeks, comparable to the responses to alum-adjuvanted toxoid. In contrast, undetectable or very low antibody responses were determined after immunisation with MS made with hydrophobic polymers. Surprisingly, large (15-60 microm) and small (1-5 microm) MS gave comparable primary antibody responses. In conclusion, the data presented confirm the feasibility of MS vaccines to induce strong, long-lasting protective antibody responses after a single immunisation. PMID:10506644

  18. Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

    PubMed Central

    Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

    2015-01-01

    The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

  19. Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

    PubMed Central

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Raze, Dominique; Bertout, Julie; Rouanet, Carine; Younes, Amena Ben; Creusy, Colette; Engle, Jacquelyn; Goldman, William E; Locht, Camille

    2006-01-01

    Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth. PMID:16839199

  20. Single oral dose toxicity test of blue honeysuckle concentrate in mice.

    PubMed

    Kim, Hyung-Soo; Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

    2015-03-01

    The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

  1. Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

    PubMed Central

    Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel

    2014-01-01

    There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131

  2. Efficacy of an albendazole feed formulation against bovine gastrointestinal nematodes including arrested larvae of Ostertagia ostertagi.

    PubMed

    Courtney, C H; Greiner, E C; Whitten, R D

    1986-01-01

    The efficacy of an albendazole feed premix formulation was compared with that of an albendazole drench suspension for control of gastrointestinal nematodes in 31 beef cattle. The premix (11 cattle) and drench suspension (9 cattle) were found to have similar efficacies at a dosage of 7.5 mg/kg of body weight. When compared with controls (11 cattle), both formulations caused significant (P less than 0.05) reductions in worm counts with an efficacy of 98% or greater against adult Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia punctata, and C pectinata. There was no significant effect against arrested 4th-stage larvae of O ostertagi. Adverse effects of albendazole treatment were not observed, and the premix formulation was readily consumed by cattle. PMID:3946888

  3. Efficacy and safety of albendazole against experimentally induced Fasciola hepatica infections in goats.

    PubMed

    Foreyt, W J

    1988-01-01

    Forty 8-week-old goats were allocated to five groups of equal size to determine the optimal dosage of albendazole against experimentally induced 14-week-old Fasciola hepatica infections. Albendazole suspension given orally at 5.0, 7.5, 10.0 and 15 mg kg-1 of body weight was 73.3, 88.2, 88.3 and 95.9% effective, respectively, when compared to untreated controls. Mean number of F. hepatica in the untreated control goats was 75.4. No signs of toxicity were observed. When albendazole was given to eight, 8-week-old goats orally at 75 mg kg-1 (five times the optimal dosage), no signs of toxicity were observed. PMID:3347986

  4. Radiation Dose from Single-Heartbeat Coronary CT Angiography Performed with a 320–Detector Row Volume Scanner1

    PubMed Central

    Elliston, Carl D.; Arai, Andrew E.; Chen, Marcus Y.; Mather, Richard; Pearson, Gregory D. N.; DeLaPaz, Robert L.; Nickoloff, Edward; Dutta, Ajoy; Brenner, David J.

    2010-01-01

    Purpose: To determine radiation doses from coronary computed tomographic (CT) angiography performed by using a 320–detector row volume scanner and evaluate how the effective dose depends on scan mode and the calculation method used. Materials and Methods: Radiation doses from coronary CT angiography performed by using a volume scanner were determined by using metal-oxide–semiconductor field-effect transistor detectors positioned in an anthropomorphic phantom physically and radiographically simulating a male or female human. Organ and effective doses were determined for six scan modes, including both 64-row helical and 280-row volume scans. Effective doses were compared with estimates based on the method most commonly used in clinical literature: multiplying dose-length product (DLP) by a general conversion coefficient (0.017 or 0.014 mSv·mGy−1·cm−1), determined from Monte Carlo simulations of chest CT by using single-section scanners and previous tissue-weighting factors. Results: Effective dose was reduced by up to 91% with volume scanning relative to helical scanning, with similar image noise. Effective dose, determined by using International Commission on Radiological Protection publication 103 tissue-weighting factors, was 8.2 mSv, using volume scanning with exposure permitting a wide reconstruction window, 5.8 mSv with optimized exposure and 4.4 mSv for optimized 100-kVp scanning. Estimating effective dose with a chest conversion coefficient resulted in a dose as low as 1.8 mSv, substantially underestimating effective dose for both volume and helical coronary CT angiography. Conclusion: Volume scanning markedly decreases coronary CT angiography radiation doses compared with those at helical scanning. When conversion coefficients are used to estimate effective dose from DLP, they should be appropriate for the scanner and scan mode used and reflect current tissue-weighting factors. © RSNA, 2010 PMID:20177085

  5. Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer

    PubMed Central

    Rischke, Hans-Christian; Meyer, Philipp Tobias; Knobe, Sven; Volgeova-Neher, Natalja; Kollefrath, Michael; Jilg, Cordula Annette; Grosu, Anca Ligia; Baltas, Dimos; Kroenig, Malte

    2016-01-01

    Purpose We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. Material and methods We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging – transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. Results Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. Conclusions Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials. PMID:27504134

  6. Pharmacokinetic Properties of Single-Dose Primaquine in Papua New Guinean Children: Feasibility of Abbreviated High-Dose Regimens for Radical Cure of Vivax Malaria

    PubMed Central

    Moore, Brioni R.; Salman, Sam; Benjamin, John; Page-Sharp, Madhu; Robinson, Leanne J.; Waita, Elizabeth; Batty, Kevin T.; Siba, Peter; Mueller, Ivo; Betuela, Inoni

    2014-01-01

    Since conventional 14-day primaquine (PMQ) radical cure of vivax malaria is associated with poor compliance, and as total dose, not therapy duration, determines efficacy, a preliminary pharmacokinetic study of two doses (0.5 and 1.0 mg/kg of body weight) was conducted in 28 healthy glucose-6-phosphate dehydrogenase-normal Papua New Guinean children, aged 5 to 12 years, to facilitate development of abbreviated high-dose regimens. Dosing was with food and was directly observed, and venous blood samples were drawn during a 168-h postdose period. Detailed safety monitoring was performed for hepatorenal function and hemoglobin and methemoglobin concentrations. Plasma concentrations of PMQ and its metabolite carboxyprimaquine (CPMQ) were determined by liquid chromatography-mass spectrometry and analyzed using population pharmacokinetic methods. The derived models were used in simulations. Both single-dose regimens were well tolerated with no changes in safety parameters. The mean PMQ central volume of distribution and clearance relative to bioavailability (200 liters/70 kg and 24.6 liters/h/70 kg) were within published ranges for adults. The median predicted maximal concentrations (Cmax) for both PMQ and CPMQ after the last dose of a 1.0 mg/kg 7-day PMQ regimen were approximately double those at the end of 14 days of 0.5 mg/kg daily, while a regimen of 1.0 mg/kg twice daily resulted in a 2.38 and 3.33 times higher Cmax for PMQ and CPMQ, respectively. All predicted median Cmax concentrations were within ranges for adult high-dose studies that also showed acceptable safety and tolerability. The present pharmacokinetic data, the first for PMQ in children, show that further studies of abbreviated high-dose regimens are feasible in this age group. PMID:24189254

  7. A comparison in young and elderly subjects of the pharmacokinetics and pharmacodynamics of single and multiple doses of benazepril.

    PubMed Central

    Macdonald, N J; Elliott, H L; Hughes, D M; Reid, J L

    1993-01-01

    1. The pharmacokinetics and pharmacodynamics of single and multiple oral doses of the ACE inhibitor benazepril were investigated in young and elderly normotensive subjects. 2. Following multiple doses the trough concentrations were significantly higher in the elderly and the areas under the plasma concentration-time curves (AUC0-24) were significantly greater, by approximately 23%. 3. The fall in blood pressure tended to be greater in the elderly subjects but this is likely to be attributable to their higher initial blood pressures, although it may reflect the small differences in pharmacokinetics. 4. The age related differences in kinetics and dynamics following multiple dosing are quantitatively similar to those obtained with single doses. However, there appears to be a quantitative difference between benazepril and other ACE inhibitors in that the age related increases were of a relatively smaller magnitude. PMID:9114904

  8. A case of acute psychosis in a patient following exposure to a single high dose of styrene.

    PubMed

    Moon, Eunsoo; Suh, Hwagyu; Lee, Byung Dae; Park, Je Min; Lee, Young Min; Jeong, Hee Jeong

    2015-09-01

    We report a case of acute psychotic symptoms following exposure to a single high dose of styrene monomer. The 24-year-old male patient showed psychotic and cognitive symptoms immediately after exposure. His psychotic symptoms included auditory hallucinations and delusions of reference. Brain magnetic resonance imaging, electroencephalography, and laboratory examinations were performed to evaluate any other causes. The clinical, neuroimaging, and laboratory review in this case suggested that the suddenly developed psychotic symptoms that led to chronic deterioration were caused by the single exposure to styrene monomer. This is the first recent report in which acute psychotic symptoms developed from a single high dose of styrene suffocation compared with previous findings showing symptoms because of long-term low-dose exposure. PMID:26184570

  9. Inhibition of prostacyclin and thromboxane biosynthesis in healthy volunteers by single and multiple doses of acetaminophen and indomethacin.

    PubMed

    Schwartz, Jules I; Musser, Bret J; Tanaka, Wesley K; Taggart, William V; Mehta, Anish; Gottesdiener, Keith M; Greenberg, Howard E

    2015-09-01

    This double-blind, randomized crossover study assessed the effect of acetaminophen (1000 mg every 8 hours) versus indomethacin (50 mg every 8 hours) versus placebo on cyclooxygenase enzymes (COX-1 and COX-2). Urinary excretion of 2,3-dinor-6-keto-PGF1α, (prostacyclin metabolite, PGI-M; COX-2 inhibition) and 11-dehydro thromboxane B2 (thromboxane metabolite, Tx-M; COX-1 inhibition) were measured after 1 dose and 5 days of dosing. Peak inhibition of urinary metabolite excretion across 8 hours following dosing was the primary end point. Mean PGI-M excretion was 33.7%, 55.9%, and 64.6% on day 1 and 49.4%, 65.1%, and 80.3% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Acetaminophen and indomethacin inhibited PGI-M excretion following single and multiple doses (P = .004 vs placebo). PGI-M excretion inhibition after 1 dose was similar for indomethacin and acetaminophen, but significantly greater with indomethacin after multiple doses (P = .006). Mean Tx-M excretion was 16.2%, 45.2%, and 86.6% on day 1 and 46.2%, 58.4%, and 92.6% on day 5 (placebo, acetaminophen, and indomethacin, respectively). Tx-M excretion inhibition following 1 dose was reduced by acetaminophen (P ≤ .003). Indomethacin reduced Tx-M excretion significantly more than acetaminophen and placebo after single and multiple doses (P ≤ .001). Acetaminophen and indomethacin inhibited COX-1 and COX-2 following a single dose, but acetaminophen was a less potent COX-1 inhibitor than indomethacin. PMID:27137142

  10. Single dose oral naproxen and naproxen sodium for acute postoperative pain (Review)

    PubMed Central

    Mason, L; Edwards, JE; Moore, RA; McQuay, HJ

    2014-01-01

    Background Postoperative pain is often poorly managed. Treatment options include a range of drug therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) of which naproxen is one. Naproxen is used to treat a variety of painful conditions including acute postoperative pain, and is often combined with sodium to improve its solubility for oral administration. Naproxen sodium 550 mg (equivalent to 500 mg of naproxen) is considered to be an effective dose for treating postoperative pain but to date no systematic review of the effectiveness of naproxen/naproxen sodium at different doses has been published. Objectives To assess the efficacy, safety and duration of action of a single oral dose of naproxen or naproxen sodium for acute postoperative pain in adults. Search strategy We searched The Cochrane Library, MEDLINE, EMBASE and the Oxford Pain Relief Database for relevant studies. Additional studies were identified from the reference list of retrieved reports. The most recent search was undertaken in July 2004. Selection criteria Included studies were randomised, double blind, placebo-controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with moderate to severe acute postoperative pain. Data collection and analysis Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over four to six hours. Relative risk estimates (RR) and the number-needed-to-treat (NNT) for at least 50% pain relief were then calculated. Information was sought on the percentage of patients experiencing any adverse event, and the number-needed-to-harm was derived. Time to remedication was also estimated. Main results Ten trials (996 patients) met the inclusion criteria: nine assessed naproxen sodium; one combined the results from two small trials of naproxen alone. Included studies scored well for methodological quality. Meta-analysis of six trials (500

  11. Single-Dose Pharmacokinetics of the CCR9 Receptor Antagonist Vercirnon in Healthy US and Japanese Subjects.

    PubMed

    Haberer, Lynda J; Hacquoil, Kimberley; Ino, Hiroko; Sakamoto, Takashi; Kanemoto, Noriaki; McSherry, Iain; Hirama, Toshiyasu

    2013-10-01

    Two randomized, single-dose, crossover studies were carried out to assess different formulations and doses of the CCR9 receptor antagonist vercirnon in healthy subjects. US study (n = 24): a five-period crossover study in healthy US subjects to assess the bioavailability of four new GlaxoSmithKline formulations compared with a "reference" formulation. Each subject received a single 500 mg dose of each of the five vercirnon formulations in a fed state. Primary pharmacokinetic (PK) endpoints were maximum plasma concentration, (Cmax ), and exposure as assessed by area under the curve (AUC). There was no significant difference in PK parameters and bioavailability between the formulations tested. Japanese study (n = 30): a four-period crossover study in healthy Japanese male subjects to assess PK and dose proportionality following single, ascending, oral doses of 250, 500, and 1,000 mg vercirnon under fasted and fed conditions. Vercirnon Cmax and AUC parameters in the fasted state increased in a less than dose proportional manner and were on average 20% higher in fed subjects compared with fasted subjects. Overall, these results support the premise that vercirnon has similar PK/safety profiles within US and Japanese populations. There was no evidence to preclude the use of the new vercirnon formulation in future studies. PMID:27121943

  12. Single dose rasburicase in the management of tumor lysis syndrome in childhood acute lymphoblastic leukemia: A case series

    PubMed Central

    Latha, S. M.; Krishnaprasadh, D.; Murugapriya, P.; Scott, J. X.

    2015-01-01

    Tumor lysis syndrome (TLS) occurs in malignancies with high proliferative potential and tumor burden, such as lymphomas and leukemias. TLS syndrome is an oncologic emergency, requiring prompt intervention. The metabolic derangements cause acute kidney failure and may lead to cardiac arrhythmias, seizures, and death. With the advent of rasburicase, a recombinant urate oxidase, there has been a decline in the TLS-mediated renal failure and the need for dialysis. The recommended regimen and doses pose a heavy financial burden for patients in developing countries like India. With data and studies proving a similar efficacy for the reduced dose and lesser number of rasburicase, we report here a case series of seven children with acute leukemias, whose TLS was managed by a single dose of rasburicase. A retrospective analysis of case records of seven children with acute lymphoblastic leukemia and TLS, admitted to our Pediatric Oncology Unit of our Hospital between the period 2011 and 2013, was done. All our patients responded to a single dose, indicating that in appropriately monitored patients, single dose followed by as-needed dosing can be cost-saving. PMID:25838646

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

    PubMed Central

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

    2015-01-01

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

  14. Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

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

    2015-01-01

    Objectives: Bufonis venonum (BV) is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP) and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. Results: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. Conclusion: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal. PMID:26998390

  15. Total Dose Effects on Single Event Transients in Linear Bipolar Systems

    NASA Technical Reports Server (NTRS)

    Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent

    2008-01-01

    Single Event Transients (SETs) originating in linear bipolar integrated circuits are known to undermine the reliability of electronic systems operating in the radiation environment of space. Ionizing particle radiation produces a variety of SETs in linear bipolar circuits. The extent to which these SETs threaten system reliability depends on both their shapes (amplitude and width) and their threshold energies. In general, SETs with large amplitudes and widths are the most likely to propagate from a bipolar circuit's output through a subsystem. The danger these SET pose is that, if they become latched in a follow-on circuit, they could cause an erroneous system response. Long-term exposure of linear bipolar circuits to particle radiation produces total ionizing dose (TID) and/or displacement damage dose (DDD) effects that are characterized by a gradual degradation in some of the circuit's electrical parameters. For example, an operational amplifier's gain-bandwidth product is reduced by exposure to ionizing radiation, and it is this reduction that contributes to the distortion of the SET shapes. In this paper, we compare SETs produced in a pristine LM124 operational amplifier with those produced in one exposed to ionizing radiation for three different operating configurations - voltage follower (VF), inverter with gain (IWG), and non-inverter with gain (NIWG). Each configuration produces a unique set of transient shapes that change following exposure to ionizing radiation. An important finding is that the changes depend on operating configuration; some SETs decrease in amplitude, some remain relatively unchanged, some become narrower and some become broader.

  16. Voluntarily exposure to a single, high dose of probiotic Escherichia coli results in prolonged colonisation.

    PubMed

    Wassenaar, T M; Beimfohr, C; Geske, T; Zimmermann, K

    2014-12-01

    The ability of probiotic Escherichia coli to colonise the human gut was determined in a volunteer study following national (German) regulations. Five persons voluntarily took a single, high dose of Symbioflor®2, which contains 6 different probiotic E. coli genotypes, to assess tolerance of the product, after which presence of E. coli in their faeces was tested for a follow-up period of 30 weeks. Intake of the product did not result in severe side effect in any of the individuals, though mild side effects were observed. Stool analysis showed that the probiotic E. coli had colonised all five persons for a period of 10 to 30 weeks (mean: 18.7 weeks, median: 25.7 weeks). In two individuals there was evidence of competition between host E. coli and probiotic E. coli, while in two others total E. coli levels increased persistently with at least a factor of 10 as a result of the received dose. In one individual, who had lacked detectable levels of faecal E. coli at the start of the post-authorisation safety study, long-term colonisation was established, first by probiotic E. coli exclusively, which were later replaced by host E. coli strains. In four out of five individuals, total E. coli faecal counts were higher on average than at the start of the experiment, while in none total levels exceeded 5×107 cfu/g. When the specific genotypes of the 6 probiotic E. coli were analysed, it was found that one and the same common genotype was responsible for prolonged colonisation in all five individuals. PMID:24985025

  17. Oral contraception does not alter single dose saquinavir pharmacokinetics in women

    PubMed Central

    Fröhlich, Margit; Burhenne, Jürgen; Martin-Facklam, Meret; Weiss, Johanna; von Wolff, Michael; Strowitzki, Thomas; Walter-Sack, Ingeborg; Haefeli, Walter E

    2004-01-01

    Aims Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. Methods Saquinavir was administered in a hard gelatin capsule formulation (Invirase®) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. Results Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17β-estradiol by −23.4 pg ml−1 (57%, 95%CI: −76% to −37.4%); progesterone by −0.25 ng ml−1 (33%, 95%CI: −45.3% to −21.5%); follicle-stimulating hormone by −4.06 U l−1 (82%, 95%CI: −96.5% to −67.7%); and luteinizing hormone by −3.49 U l−1 (74%, 95%CI: −93 to −54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l−1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. Conclusions There

  18. Single dose oral tiaprofenic acid for acute postoperative pain in adults

    PubMed Central

    Moore, R Andrew; Derry, Sheena; Moore, Maura; McQuay, Henry J

    2014-01-01

    Background Tiaprofenic acid is a a non-steroidal anti-inflammatory drug (NSAID). It is widely available around the world, with indications for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, periarticular disorders, and strains and sprains. This review sought to evaluate the efficacy and safety of oral tiaprofenic acid in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. Objectives To assess the efficacy of single dose oral tiaprofenic acid in acute postoperative pain, and any associated adverse events. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to June 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered tiaprofenic acid in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We planned to use area under the “pain relief versus time” curve to derive the proportion of participants with tiaprofenic acid experiencing at least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. Main results Not one of eleven studies identified by the searches and examined in detail studied oral tiaprofenic acid against placebo in patients with established postoperative pain and therefore no results are available. Authors’ conclusions In the absence of evidence of efficacy for oral tiaprofenic acid in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly

  19. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection.

    PubMed Central

    Morse, G D; Fischl, M A; Shelton, M J; Cox, S R; Driver, M; DeRemer, M; Freimuth, W W

    1997-01-01

    Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 (HIV-1) that is currently being evaluated in combination regimens with various nucleoside analogs, including didanosine. Due to the pH-dependent solubility of delavirdine, the buffering agents in didanosine formulations may reduce delavirdine absorption. To evaluate the potential interaction between these agents, 12 HIV-infected patients (mean [+/- standard deviation] CD4+ cell count, 304 +/- 213/mm3) were enrolled in a three-way crossover single-dose study. Didanosine (125 to 200 mg given as buffered tablets) and delavirdine mesylate (400 mg) pharmacokinetics were evaluated when each drug was given alone (treatments A and B, respectively), when the two drugs were given concurrently (treatment C), and when didanosine was given 1 h after delavirdine (treatment D). Delavirdine exposure was reduced by concurrent administration of didanosine. The maximum drug concentration in serum (Cmax) was reduced from 7.22 +/- 4.0 to 3.51 +/- 1.9 microM, and the area under the concentration-time curve from 0 h to infinity (AUC0-->infinity) was reduced from 22.5 +/- 14 to 14 +/- 5.7 microM.h. The extent of N-dealkylation, as indicated by the ratio of the N-dealkylated delavirdine AUC0-->infinity to the delavirdine AUC0-->infinity, was unchanged across study treatments (P = 0.708). Reductions in didanosine exposure were observed during concurrent administration with delavirdine with a Cmax reduction from 4.65 +/- 2.0 to 3.22 +/- 0.59 microM and an AUC0-->infinity reduction from 7.93 +/- 3.9 to 6.54 +/- 2.3 microM.h. Thus, concurrent administration of delavirdine and didanosine may reduce the AUC0-->infinity of both drugs, although the clinical significance of this reduction is unknown. Administration of delavirdine 1 h before didanosine avoided the interaction. Due to the single-dose nature of this study, these findings require further evaluation at steady

  20. Single-Dose Replication-Defective VSV-based Nipah Virus Vaccines Provide Protection from Lethal Challenge in Syrian Hamsters

    PubMed Central

    Lo, Michael K.; Bird, Brian H.; Chattopadhyay, Anasuya; Drew, Clifton P.; Martin, Brock E.; Coleman, Joann D.; Rose, John K.; Nichol, Stuart T.; Spiropoulou, Christina F.

    2013-01-01

    Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans. PMID:24184127

  1. A comparison of the dose distributions from three proton treatment planning systems in the planning of meningioma patients with single-field uniform dose pencil beam scanning.

    PubMed

    Doolan, Paul J; Alshaikhi, Jailan; Rosenberg, Ivan; Ainsley, Chris G; Gibson, Adam; D'Souza, Derek; Bentefour, El Hassane; Royle, Gary

    2015-01-01

    With the number of new proton centers increasing rapidly, there is a need for an assessment of the available proton treatment planning systems (TPSs). This study compares the dose distributions of complex meningioma plans produced by three proton TPSs: Eclipse, Pinnacle3, and XiO. All three systems were commissioned with the same beam data and, as best as possible, matched configuration settings. Proton treatment plans for ten patients were produced on each system with a pencil beam scanning, single-field uniform dose approach, using a fixed horizontal beamline. All 30 plans were subjected to identical dose constraints, both for the target coverage and organ at risk (OAR) sparing, with a consistent order of priority. Beam geometry, lateral field margins, and lateral spot resolutions were made consistent across all systems. Few statistically significant differences were found between the target coverage and OAR sparing of each system, with all optimizers managing to produce plans within clinical tolerances (D2 < 107% of prescribed dose, D5 < 105%, D95 > 95%, D99 > 90%, and OAR maximum doses) despite strict constraints and overlapping structures. PMID:25679158

  2. Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

    SciTech Connect

    Yuan, Lulin Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David; Jiang, Yuliang; Ge, Yaorong

    2014-02-15

    Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined

  3. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    SciTech Connect

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Katoh, Yutai; Wirth, Brian D; Snead, Lance Lewis

    2016-01-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (~90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutron irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S–W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage. This provides insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.

  4. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Katoh, Yutai; Snead, Lance L.; Wirth, Brian D.

    2016-03-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (∼90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutron irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S-W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage, providing insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.

  5. Defect evolution in single crystalline tungsten following low temperature and low dose neutron irradiation

    DOE PAGESBeta

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Katoh, Yutai; Wirth, Brian D; Snead, Lance Lewis

    2016-01-01

    The tungsten plasma-facing components of fusion reactors will experience an extreme environment including high temperature, intense particle fluxes of gas atoms, high-energy neutron irradiation, and significant cyclic stress loading. Irradiation-induced defect accumulation resulting in severe thermo-mechanical property degradation is expected. For this reason, and because of the lack of relevant fusion neutron sources, the fundamentals of tungsten radiation damage must be understood through coordinated mixed-spectrum fission reactor irradiation experiments and modeling. In this study, high-purity (110) single-crystal tungsten was examined by positron annihilation spectroscopy and transmission electron microscopy following low-temperature (~90 °C) and low-dose (0.006 and 0.03 dpa) mixed-spectrum neutronmore » irradiation and subsequent isochronal annealing at 400, 500, 650, 800, 1000, 1150, and 1300 °C. The results provide insights into microstructural and defect evolution, thus identifying the mechanisms of different annealing behavior. Following 1 h annealing, ex situ characterization of vacancy defects using positron lifetime spectroscopy and coincidence Doppler broadening was performed. The vacancy cluster size distributions indicated intense vacancy clustering at 400 °C with significant damage recovery around 1000 °C. Coincidence Doppler broadening measurements confirm the trend of the vacancy defect evolution, and the S–W plots indicate that only a single type of vacancy cluster is present. Furthermore, transmission electron microscopy observations at selected annealing conditions provide supplemental information on dislocation loop populations and visible void formation. This microstructural information is consistent with the measured irradiation-induced hardening at each annealing stage. This provides insight into tungsten hardening and embrittlement due to irradiation-induced matrix defects.« less

  6. Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

    PubMed

    Leary, A; Barthe, L; Clavel, T; Sanchez, C; Oulmi-Castel, M; Paillard, B; Edmond, J M; Brunner, V

    2016-01-01

    Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration. PMID:25989284

  7. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects

    PubMed Central

    Sakurai, Yuuichi; Nishimura, Akira; Kennedy, Gale; Hibberd, Mark; Jenkins, Richard; Okamoto, Hiroyuki; Yoneyama, Tomoki; Jenkins, Helen; Ashida, Kiyoshi; Irie, Shin; Täubel, Jörg

    2015-01-01

    OBJECTIVES: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects. METHODS: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1–120 mg in Japan and 1–40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH). RESULTS: Plasma concentration–time profiles of TAK-438 at all dose levels showed rapid absorption (median Tmax up to 2 h). Estimated mean elimination half-life was up to 9 h. Exposure was slightly greater than dose proportional. No clear difference in TAK-438 pharmacokinetics was observed between Japanese and non-Japanese subjects. Acid suppression was dose dependent and similar in both studies. The 24-h intragastric pH ≥4 holding time ratio with 40 mg TAK-438 was 92% in Japan and 87% in the UK. TAK-438 was well tolerated, with no adverse events reported in Japanese subjects; 10 of 63 UK subjects experienced 12 treatment-emergent adverse events (non-serious). Increases in serum gastrin and pepsinogen I and II concentrations were observed at doses ≥10 mg, but there were no changes in alanine aminotransferase concentrations. CONCLUSIONS: Single oral doses of TAK-438 20–120 mg caused rapid, profound, and 24-h suppression of gastric acid secretion in healthy male subjects, regardless of geographical region, and TAK-438 was well tolerated at all doses studied, making it a potential alternative to proton pump inhibitors for the treatment of acid-related disorders. PMID:26111126

  8. Single dose pharmacokinetics, pharmacodynamics, tolerability and safety of BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein

    PubMed Central

    Boettcher, Michael-Friedrich; Heinig, Roland; Schmeck, Carsten; Kohlsdorfer, Christian; Ludwig, Matthias; Schaefer, Anja; Gelfert-Peukert, Sabine; Wensing, Georg; Weber, Olaf

    2012-01-01

    AIMS To determine pharmacokinetics (PK), pharmacodynamics (PD), tolerability and safety of BAY 60–5521, a potent inhibitor of cholesteryl ester transfer protein (CETP). METHODS The first in man (FIM) study investigated the safety, tolerability, pharmacodynamics and pharmacokinetics in healthy male subjects following administration of single oral doses. The study was performed using a randomized, single-blind, placebo-controlled, single dose-escalation design. Thirty-eight young healthy male subjects (aged 20–45 years) received an oral dose of 5, 12.5, 25 or 50 mg BAY 60–5521 (n = 28) or were treated with a placebo (n = 10). RESULTS In all four dose steps, only one adverse event (25 mg; mild skin rash) was considered drug related. Clinical laboratory parameters showed no clinically relevant changes. A clear dose-dependent CETP inhibition could be demonstrated starting at a dose of 5 mg. At a dose of 25 mg, a CETP inhibition >50% over 18 h was observed. After 50 mg, CETP inhibition >50% lasted more than 50 h. Twenty-four h after administration mean HDL-C-values showed a nearly dose-proportional increase. Following administration of 50 mg, a significant HDL-C increase of about 30% relative to baseline values was found. BAY 60–5521 was slowly absorbed reaching maximum concentrations in plasma after 4 to 6 h. The disposition in plasma was multi-exponential with an estimated mean terminal half-life of 76 to 144 h. CONCLUSIONS BAY 60–5521 was clinically safe and well tolerated. No effects on heart rate, blood pressure and ECG recordings were observed during the study. A clear pharmacodynamic effect on CETP inhibition and HDL could be demonstrated. PMID:21838789

  9. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects.

    PubMed

    Winter, Helen; Egizi, Erica; Murray, Stephen; Erondu, Ngozi; Ginsberg, Ann; Rouse, Doris J; Severynse-Stevens, Diana; Pauli, Elliott

    2015-02-01

    This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (Cmax), area under the concentration-time curve to the last available concentration time point (AUC0-t), and AUC extrapolated to infinity (AUC0-inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the Cmax, AUC0-t, and AUC0-inf of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The Cmax, AUC0-t, and AUC0-inf of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier NCT02216331

  10. Histopathological changes in rat liver after a single high dose of aluminium.

    PubMed

    Bogdanović, Milka; Janeva, Ana Begić; Bulat, Petar

    2008-06-01

    Aluminium (Al) exposure may affect the liver of experimental animals. This investigation aimed at evaluating morphological changes in rat liver after a single high dose of Al (as metallic powder suspension). A total of forty female Wistar rats were divided in one exposed and one control group, 20 rats each. The exposed rats received 0.5 mL of sterile physiological suspension of fine Al powder in the concentration of 100 mg mL-1 intraperitoneally (50 mg Al per rat). After 7 weeks all animals were killed (by exsanguination from the abdominal aorta in ether anaesthesia). Liver aluminium was analysed using electrothermal atomic absorption spectrometry. For light microscopy the liver tissue was stained with hematoxylin and eosin, and for histochemical analysis with aurin threecarbocsillic acid (aluminon). Liver Al level was markedly higher in the exposed (37.1 microg g-1) than in control rats (0.71 microg g-1). The exposed rats showed crystalloid Al inclusions in the capsular, subcapsular, and portal liver tissue. The basic liver structure remained intact. Slightly multiplied bile ductuli were found in 16 of 20 exposed and in 8 of 20 control rats. Three exposed rats had mycrovesicular steatosis. The peritoneum and Glisson's capsule showed strong macrophage infiltration and a foreign-body-like reaction with multiple giant macrophages containing Al crystalloid inclusions. Although this reaction was a defense against the metal, some Al passed this barrier and entered the liver tissue, exerting toxic effects in bile ductuli and hepatocytes. PMID:18573746

  11. Effects of a single dose of menadione on the intestinal calcium absorption and associated variables.

    PubMed

    Marchionatti, Ana M; Díaz de Barboza, Gabriela E; Centeno, Viviana A; Alisio, Arturo E; Tolosa de Talamoni, Nori G

    2003-08-01

    The effect of a single large dose of menadione on intestinal calcium absorption and associated variables was investigated in chicks fed a normal diet. The data show that 2.5 micro mol of menadione/kg of b.w. causes inhibition of calcium transfer from lumen-to-blood within 30 min. This effect seems to be related to oxidative stress provoked by menadione as judged by glutathione depletion and an increment in the total carbonyl group content produced at the same time. Two enzymes presumably involved in calcium transcellular movement, such as alkaline phosphatase, located in the brush border membrane, and Ca(2+)- pump ATPase, which sits in the basolateral membrane, were also inhibited. The enzyme inhibition could be due to alterations caused by the appearance of free hydroxyl groups, which are triggered by glutathione depletion. Addition of glutathione monoester to the duodenal loop caused reversion of the menadione effect on both intestinal calcium absorption and alkaline phosphatase activity. In conclusion, menadione shifts the balance of oxidative and reductive processes in the enterocyte towards oxidation causing deleterious effects on intestinal Ca(2+) absorption and associated variables, which could be prevented by administration of oral glutathione monoester. PMID:12948877

  12. A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis

    PubMed Central

    Thulkar, Jyoti; Kriplani, Alka; Agarwal, Nutan

    2012-01-01

    Objective: To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis. Materials and Methods: This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard. Results: At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs. Conclusion: Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis. PMID:22529484

  13. [MAXIMUM SINGLE DOSE OF COLLOIDAL SILVER NEGATIVELY AFFECTS ERYTHROPOIESIS IN VITRO].

    PubMed

    Tishevskayal, N V; Zakharovl, Y M; Bolotovl, A A; Arkhipenko, Yu V; Sazontova, T G

    2015-01-01

    Erythroblastic islets (EI) of rat bone marrow were cultured for 24 h in the presence of silver nanoparticles (1.07 · 10(-4) mg/ml; 1.07 · 10(-3) mg/ml; and 1.07 · 10(-2) mg/mL). The colloidal silver at 1.07 · 10(-3) mg/ml concentration inhibited the formation of new Elby disrupting contacts of bone marrow macrophages with CFU-E (erythropoiesis de novo) by 65.3% (p < 0.05). Colloidal silver nanoparticles suppressed the reconstruction of erythropoiesis and inhibited the formation of new EI by disrupting contacts of CFU-E and central macrophages with matured erythroidal "crown" (erythropoiesis de repeto). The colloidal silver concentration of 1.07 · 10(-3) mg/ml in the culture medium also reduced the number of self-reconstructing EI by 67.5% (p <0.05), whereas 1.07 · 10(-2) mg/ml colloidal silver reduced this value by 93.7% (p < 0.05). Silver nanoparticles retarded maturation of erythroid cells at the stage of oxiphylic normoblast denucleation: 1.07 · 10(-3) mg/ml colloidal silver increased the number of mature El by 53% (p < 0.05). The retardation of erythropoiesis by colloidal silver in concentration equivalent to the maximum single dose is related to the effect of silver nanoparticles rather than glycerol present in the colloidal suspension. PMID:26591205

  14. A Single Human Papillomavirus Vaccine Dose Improves B Cell Memory in Previously Infected Subjects.

    PubMed

    Scherer, Erin M; Smith, Robin A; Gallego, Daniel F; Carter, Joseph J; Wipf, Gregory C; Hoyos, Manuela; Stern, Michael; Thurston, Tate; Trinklein, Nathan D; Wald, Anna; Galloway, Denise A

    2016-08-01

    Although licensed human papillomavirus (HPV) vaccines are most efficacious in persons never infected with HPV, they also reduce infection and disease in previously infected subjects, indicating natural immunity is not entirely protective against HPV re-infection. The aim of this exploratory study was to examine the B cell memory elicited by HPV infection and evaluate whether vaccination merely boosts antibody (Ab) levels in previously infected subjects or also improves the quality of B cell memory. Toward this end, the memory B cells (Bmem) of five unvaccinated, HPV-seropositive subjects were isolated and characterized, and subject recall responses to a single HPV vaccine dose were analyzed. Vaccination boosted Ab levels 24- to 930-fold (median 77-fold) and Bmem numbers 3- to 27-fold (median 6-fold). In addition, Abs cloned from naturally elicited Bmem were generally non-neutralizing, whereas all those isolated following vaccination were neutralizing. Moreover, Ab and plasmablast responses indicative of memory recall responses were only observed in two subjects. These results suggest HPV vaccination augments both the magnitude and quality of natural immunity and demonstrate that sexually active persons could also benefit from HPV vaccination. This study may have important public policy implications, especially for the older 'catch-up' group within the vaccine's target population. PMID:27423190

  15. Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus.

    PubMed

    Mire, Chad E; Matassov, Demetrius; Geisbert, Joan B; Latham, Theresa E; Agans, Krystle N; Xu, Rong; Ota-Setlik, Ayuko; Egan, Michael A; Fenton, Karla A; Clarke, David K; Eldridge, John H; Geisbert, Thomas W

    2015-04-30

    The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV. PMID:25853476

  16. Effect of a single injection of high-dose FK506 on lung transplantation in rats.

    PubMed

    Sano, Y; Maruyama, S; Aoe, M; Date, H; Shimizu, N

    1996-01-01

    Orthotopic left lung grafts from Brown Norway (BN) donors were transplanted to Lewis (LEW) rat recipients which had been treated with a single dose of FK506 10mg/kg body weight intramuscularly on postoperative day 3. Although the lungs were rejected with a median survival time of 7 days, with a range of 6-8 days in the untreated controls, maximum survival was prolonged to 60 days. The major adverse effects of this therapy were reduction of feeding, loss of body weight, and diarrhea. One of the 7 rats died on the 21st postoperative day due to anorexia. The effects of this therapy were investigated by histopathological examination and flow cytometric analysis using monoclonal antibodies against rat lymphocytes: OX-39 (anti-interleukin 2 receptor (IL-2R)) and OX-6 (anti-class II MHC). Histopathologically, the lung allografts showed mild perivascular and peribronchiolar cuffs of mononuclear cells, while marked reduction of the thymic medulla with FK506 treatment was also observed. Flow cytometric analysis of the transplanted lung showed no significant changes. Regarding the thymus, the percentages of positive cells labeled with OX-39 and OX-6 were significantly suppressed after this treatment. In the spleen, the number of OX-6-positive cells significantly decreased. The results using this therapy thus suggest that the suppression of IL-2R and MHC class II expression was systemically maintained for a long time. PMID:9017963

  17. Single dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus

    PubMed Central

    Geisbert, Joan B.; Latham, Theresa E.; Agans, Krystle N.; Xu, Rong; Ota-Setlik, Ayuko; Egan, Michael A.; Fenton, Karla A.; Clarke, David K.; Eldridge, John H.; Geisbert, Thomas W.

    2015-01-01

    The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus1. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal hemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in nearly 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primate (NHPs) against ZEBOV2. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately ten-fold lower vaccine-associated viremia compared to the first generation vaccine and both provided complete, single dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV. PMID:25853476

  18. Single-dose pharmacokinetics of bupropion hydrobromide and metabolites in healthy adolescent and adult subjects.

    PubMed

    Oh, D Alexander; Crean, Christopher S

    2015-09-01

    Data from 2 pediatric single-dose studies, conducted at the same center, were combined to evaluate exposure levels of bupropion and metabolites in adolescents 12-17 years old, compared with adults > 18 years. Pharmacokinetic analyses of bupropion and its metabolites were performed using normalization and pharmacological/convulsive weighting methods on exposure. When compared with adults (>18 years), subjects 12-14 years had an increase in weight-normalized exposure to bupropion (ie, Cmax , 78%; AUC0-t , 83%; and AUCinf , 85%). Variability in this younger age group was also higher, with observations of a 3- to 4-fold increase in exposure. When the changes in metabolites were accounted within pharmacological and convulsive-weighted exposures, the relative ratio of 12-14 years to adults in body weight-normalized Cmax was 127% and 110%, respectively. Subjects 15-17 years did not exhibit a difference in exposure compared with adults. The influence of age on bupropion pharmacokinetics demonstrates that, in general, healthy adolescent subjects cannot be considered smaller healthy adult subjects; the increase in exposure is inversely related to age and appears to be solely associated with bupropion, not with its metabolites. Because there are no clinical safety and efficacy data of bupropion in adolescents, this data may shift its risk-benefit profile. PMID:27137143

  19. Adhesion of leukocytes to dermal endothelial cells is induced after single-dose, but reduced after repeated doses of UVA.

    PubMed

    Heckmann, M; Pirthauer, M; Plewig, G

    1997-12-01

    Approximately 20-50% of ultraviolet A (UVA) irradiation delivered to the skin surface may reach the human dermal microvascular endothelial cells (HDMEC) that play a pivotal role in cellular inflammatory tissue; however, the pathophysiologic role of HDMEC in UVA-induced skin changes is largely unknown. Based on previous in vivo and in vitro studies revealing UVA-induced expression of endothelial adhesion molecules, we studied isolated HDMEC under various conditions in order to further delineate the impact of UVA on these cells. The expression of cell adhesion molecules was determined by flow cytometry and the resulting changes of stable adhesion of leukocytes to endothelial cells were quantitated for granulocytes, lymphocytes, and monocytes using a newly developed multicellular adhesion assay. Additionally, antibody blocking experiments were performed to delineate the role of individual cell adhesion molecules in UVA-induced leukocyte adherence. High-dose polychromatic UVA (25 J per cm2, maximal emission at 375 nm) induced intercellular adhesion molecule-1 and E-selectin with different kinetics but correlating the adhesion of leukocyte subsets. This effect subsided, however, in the course of 3-6 daily applied UVA doses. Moreover, pro-inflammatory cytokine challenge by tumor necrosis factor-alpha and interleukin-1-alpha resulted in significantly weaker induction of intercellular adhesion molecule-1 and E-selectin in repeatedly UVA-exposed HDMEC. Differential quantitation of peripheral blood derived granulocytes, lymphocytes, and monocytes revealed reduced adhesion particularly of lymphocytes followed by monocytes and granulocytes compared with leukocyte adhesion to nonirradiated but cytokine-stimulated HDMEC. It is concluded that UVA substantially influences endothelial cell adhesion molecules expression and thus directly interferes with leukocyte adhesion to endothelial cells. Divergent UVA-induced effects in this respect can be attributed to the mode of UV exposure

  20. A tolerance study of single and multiple dosing of the selective dopamine uptake inhibitor GBR 12909 in healthy subjects.

    PubMed

    Søgaard, U; Michalow, J; Butler, B; Lund Laursen, A; Ingersen, S H; Skrumsager, B K; Rafaelsen, O J

    1990-10-01

    GBR 12909 selectively blocks dopamine uptake and its biochemical and pharmacological profiles suggest that it may possess antidepressant activity and be of value in treatment of Parkinson's disease. The tolerance, pharmacokinetics and influence on psychomotor performance of GBR 12909 were investigated in a randomized placebo-controlled double-blind study. Four healthy subjects were administered oral single doses of 100, 200 and 300 mg GBR 12909 and placebo, and four other healthy subjects received, 50, 100 and 150 mg GBR 12909 and placebo once daily for 7 days. The intermediate and highest doses resulted in mild to moderate side-effects such as difficulties in concentrating, asthenia, feeling of drug influence and palpitations. No changes were observed in haematological and clinico-chemical parameters. A dose-related effect on ECG was observed with a slight reduction of the T-wave amplitude. No signs of arrhythmia or decompensation during exercise until exhaustion were observed. Psychomotor performance indicated dose-related sedation in the single-dose study. Only minor deviations from first order kinetics were observed. Elimination half-life was estimated at 1-2 days. Steady-state serum concentrations of GBR 12909 appeared to be attained within 1 week. Based on the results of this study, the estimated therapeutic doses are expected to be well-tolerated in patients. PMID:2150527

  1. Voriconazole Disposition After Single and Multiple, Oral Doses in Healthy, Adult Red-tailed Hawks ( Buteo jamaicensis ).

    PubMed

    Gentry, Jordan; Montgerard, Christy; Crandall, Elizabeth; Cruz-Espindola, Crisanta; Boothe, Dawn; Bellah, Jamie

    2014-09-01

    Voriconazole is effective for treatment of aspergillosis, a common disease in captive red-tailed hawks ( Buteo jamaicensis ). To determine the disposition and safety of voriconazole after single and multiple, oral doses, 12 adult red-tailed hawks were studied in 2 phases. In phase 1, each bird received a single dose of voriconazole solution (10 mg/kg) by gavage. Blood samples were collected at 0, 0.5, 1, 3, 6, 9, 12, 16, 24, and 36 hours after treatment. In phase 2, each of 8 birds received voriconazole oral solution at 10 mg/kg PO q12h for 14 days. Plasma samples were collected on days 0, 5, and 10 and after the final dose and were processed as in phase 1. Plasma samples were submitted for analysis of voriconazole levels by high-performance liquid chromatography and ultraviolet spectrophotometry and for measurement of selected plasma biochemical parameters. After single dosing, voriconazole concentrations reached a (mean ± SD) peak (Cmax) of 4.7 ± 1.3 μg/mL at 2.0 ± 1.2 hours. The disappearance half-life (t1/2) was 2.8 ± 0.7 hours, and the mean residence time (MRT) was 4.6 ± 0.9 hours. After the last dose at 14 days, the mean Cmax of voriconazole was 4.5 ± 2.7 μg/mL at 2.4 ± 1.1 hours. The t1/2 was 2.1 ± 0.8 hours, and the MRT was 3.5 ± 1.1 hours. Although concentrations of several plasma biochemical parameters were significantly different at study end compared with prestudy concentrations, only plasma creatine kinase activity was outside the reference range. No adverse reactions were observed in any of the birds. After both single and multiple dosing at 10 mg/kg, voriconazole concentrations exceeded the minimum inhibitory concentration to inhibit 90% (MIC90) of Aspergillus species (1 μg/mL) by at least fourfold and remained above the MIC90 for 8.8 ± 1.1 hours after single dosing versus 6.5 ± 1.5 hours after multiple dosing (P = .003). This difference suggests that more frequent dosing (eg, up to q8h) may be necessary to maintain target

  2. REPRODUCTIVE TOXICITY OF A SINGLE DOSE OF 1,3-DINITROBENZENE IN TWO AGES OF YOUNG ADULT MALE RATS

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-Dinitrobenzene (M-DNB). oung adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, ...

  3. Hookworm-related cutaneous larva migrans in northern Brazil: resolution of clinical pathology after a single dose of ivermectin.

    PubMed

    Schuster, Angela; Lesshafft, Hannah; Reichert, Felix; Talhari, Sinesio; de Oliveira, Silas Guedes; Ignatius, Ralf; Feldmeier, Hermann

    2013-10-01

    To assess the effect of ivermectin on the morbidity caused by hookworm-related cutaneous larva migrans in patients in hyperendemic areas, we treated 92 patients (with 441 tracks in total) from Manaus, Brazil, with single-dose ivermectin (200 µg/kg). Four weeks later, patients had 60 tracks, and the associated morbidity improved significantly. PMID:23811416

  4. 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

    ... 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, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND...

  5. [Evaluation of action, efficacy, and onset dynamics of a single dose of alginates in patients with heartburn and GERD].

    PubMed

    Bordin, D S; Masharova, A A; Firsova, L D; Kozhurina, T S; Safonova, O V

    2009-01-01

    We conducted a crossover study, in which the efficacy and the onset of action of a single dose of Gaviscon (suspension) and Gaviscon forte (suspension) in 52 patients with heartburn of moderate intensity and gastroesophageal reflux disease (GERD) have been investigated. The average age of the patients was 44.0 +/- 17.3-years-old. The patients have undergone clinical evaluation of intensity of GERD symptoms and psychological assessment (questionnaires SF-36, SMOL, LOBI). Alginates' effects and qualities were evaluated using stopwatch technique, clinical examination, and organoleptic assessment. Primary sensation of a cooling (soothing) effect after use of a single dose of Gaviscon has been reported in 65.7 seconds (on average), and Gaviscon forte--in 66.1 seconds. Fourty three (82.7%) patients with heartburn have described the effects of both medications as "instant" cooling effects. Heartburn was relieved in 3.3 minutes in all patients after a single dose of Gaviscon, and in 3.6 minutes in 51 (98.1%) patients who have received a single dose of Gaviscon forte. Organoleptic qualities averaged at 3.6 points (on a scale of 1-5) for Gaviscon, and at 3.5 points for Gaviscon forte. Assessment of mental status of the patients suggested that a "delayed" effect of the medications in relieving heartburn in some patients may have occurred due to possible physical disadaptation. PMID:19960998

  6. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  7. Trophic transfer of nano-TiO2 in a paddy microcosm: A comparison of single-dose versus sequential multi-dose exposures.

    PubMed

    Kim, Jung In; Park, Hyung-Geun; Chang, Kwang-Hyeon; Nam, D H; Yeo, Min-Kyeong

    2016-05-01

    In the present study, replicated paddy microcosm systems were used to investigate the environmental fate and trophic transfer of titanium nanoparticles (NPs) over a period of 14 days. Most TiO2 NPs immediately settled down in the sediment, and high accumulations of nano TiO2 in the sandy loam sediment and biofilm were observed. The test organisms (quillworts, water dropworts, duckweeds, biofilms, river snails, and Chinese muddy loaches) and environmental media (freshwater, sandy loam sediment) were exposed to sequential low doses (2 mg/L at 1 h, 4 days, and 9 days) or a single high-dose (6 mg/L) of TiO2 NPs. The bioconcentration factors (BCFs) of nano-TiO2 in biofilms, quillworts, duckweeds, and Chinese muddy loaches were higher in the sequential multi-dose group than in the single-dose group. Chinese muddy loaches showed higher bioaccumulation factors (BAFs) over their prey than river snails. The difference in the carbon isotope ratios between Chinese muddy loaches and river snails was less than 2‰, and an approximately 4‰ difference in the stable nitrogen isotope ratio was observed in the two aquatic predators from their major prey (e.g., biofilms or particulate organic matter). The trophic levels between biofilms and river snails and between biofilms and Chinese muddy loaches were 2.8 and 2.4 levels, respectively. These results indicate that these two predators consumed biofilm and other alternative preys at a higher level than biofilm. Although the trophic transfer rates of TiO2 are generally low, relatively higher biomagnification factors (BMFs) were found in Chinese muddy loaches (0.04-0.05) than in river snails (0.01-0.02). These results suggest that TiO2 NPs show greater movement in the sediment than in the water and that TiO2 NPs can be retained through aquatic food chains more after a sequential low-dose exposure than after a single high-dose exposure. PMID:26854701

  8. Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

    PubMed Central

    Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

  9. Effectiveness Evaluation of Levamisole, Albendazole, Ivermectin, and Vernonia amygdalina in West African Dwarf Goats

    PubMed Central

    Adediran, Oyeduntan A.; Uwalaka, Emmanuel C.

    2015-01-01

    Anthelmintic drug resistance has led to the search for alternatives in controlling helminth infections. Fifty West African Dwarf goats without history of anthelmintic treatment were divided equally into five groups. Group A was treated with ivermectin injection subcutaneously, group B with levamisole subcutaneously, group C with albendazole orally, and group D with aqueous extract of Vernonia amygdalina and group E was untreated control. Faecal samples were collected before treatment from each animal and larval culture was carried out. Faecal egg count reduction (FECR) test was carried out for each group and the data analysed using FECR version 4 to calculate percent reduction in faecal egg count. Predominant helminth infections from larval culture were Haemonchus contortus (70%), Trichostrongylus spp. (61%), and Oesophagostomum spp. (56%). Mixed infection was present in all the animals. From the FECR test Vernonia amygdalina extract was more effective against helminths (100%), compared to ivermectin 96%, levamisole 96%, and albendazole 99%. The lower 95% confidence limit was 89 for ivermectin and levamisole and 91 for albendazole. There is low resistance to ivermectin and levamisole and susceptibility to albendazole while V. amygdalina has great potentials that could be explored for the treatment of helminth diseases in goats. PMID:26579232

  10. Effectiveness Evaluation of Levamisole, Albendazole, Ivermectin, and Vernonia amygdalina in West African Dwarf Goats.

    PubMed

    Adediran, Oyeduntan A; Uwalaka, Emmanuel C

    2015-01-01

    Anthelmintic drug resistance has led to the search for alternatives in controlling helminth infections. Fifty West African Dwarf goats without history of anthelmintic treatment were divided equally into five groups. Group A was treated with ivermectin injection subcutaneously, group B with levamisole subcutaneously, group C with albendazole orally, and group D with aqueous extract of Vernonia amygdalina and group E was untreated control. Faecal samples were collected before treatment from each animal and larval culture was carried out. Faecal egg count reduction (FECR) test was carried out for each group and the data analysed using FECR version 4 to calculate percent reduction in faecal egg count. Predominant helminth infections from larval culture were Haemonchus contortus (70%), Trichostrongylus spp. (61%), and Oesophagostomum spp. (56%). Mixed infection was present in all the animals. From the FECR test Vernonia amygdalina extract was more effective against helminths (100%), compared to ivermectin 96%, levamisole 96%, and albendazole 99%. The lower 95% confidence limit was 89 for ivermectin and levamisole and 91 for albendazole. There is low resistance to ivermectin and levamisole and susceptibility to albendazole while V. amygdalina has great potentials that could be explored for the treatment of helminth diseases in goats. PMID:26579232

  11. A comparative clinical trial of albendazole versus metronidazole in children with giardiasis.

    PubMed

    Misra, P K; Kumar, A; Agarwal, V; Jagota, S C

    1995-07-01

    The adverse effects and treatment failures to some of the currently recommended drugs for giardia infection have given rise to the need for alternative antigiardial agents. In an open, randomized parallel group study, the safety and efficacy of albendazole was compared with metronidazole for the treatment of giardiasis in children. Sixty four children of age ranging from 2-12 years was randomized to receive either albendazole suspension 400 mg daily for 5 days or metronidazole suspension 400 mg daily for 5 days or metronidazole suspension 7.5 mg/Kg thrice daily for 5 days. The mean days required for cure, as evident by absence of cysts and/or trophozoites in the stool specimen, were 3.7 +/- 1.4 and 4.5 +/- 1.1 days, respectively for children on albendazole and metronidazole therapy. Six children on metronidazole therapy developed anorexia 2 to 4 days after the treatment. Albendazole proved as effective as metronidazole in the treatment of giardia infection in children with the added advantage of the absence of anorexia. PMID:8617554

  12. Comparative efficacy of clorsulon and albendazole against Fasciola hepatica in cattle.

    PubMed

    Kilgore, R L; Williams, M L; Benz, G W; Gross, S J

    1985-07-01

    In a dosage-confirmation trial, anthelmintic activities of clorsulon and albendazole against Fasciola hepatica were evaluated and compared. Twenty-eight cattle (8 to 12 months old) with natural F hepatica infections were randomly allotted to 4 groups of 7 cattle each: group 1, no treatment (controls); group 2, clorsulon suspension given orally at 3.5 mg/kg of body weight; group 3, clorsulon suspension given orally at 7 mg/kg; and group 4, albendazole paste given orally at 10 mg/kg. At necropsies, performed 7 and 8 days after treatment, control cattle harbored a geometric mean of 133.2 F hepatica, 16.0 of which were immature. Clorsulon administered at 3.5 mg/kg or 7 mg/kg resulted in greater than 99% removal of F hepatica, including immatures. Albendazole treatment resulted in a 76% overall reduction in F hepatica, including a 91% reduction of immatures. Fascioloides magna also were found in the cattle, but neither clorsulon nor albendazole caused significant reductions of the parasite. Adverse reactions to the 2 drugs were not observed. PMID:4026039

  13. Increasing the solubility characteristics of albendazole with dimethyl-beta-cyclodextrin.

    PubMed

    Kata, M; Schauer, M

    1991-01-01

    Albendazole is a veterinary anthelminthic drug with excellent effect. Since it is only slightly soluble in water, it is processed in a suspension dosage form as a drench. The solubility and bioavailability of the pharmacon were successfully increased with cyclodextrin derivatives. PMID:1872189

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

    PubMed

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

    2014-02-01

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

  15. Single- and multiple-dose tolerability and pharmacokinetics of the CRTH2 antagonist setipiprant in healthy male subjects.

    PubMed

    Sidharta, Patricia N; Diamant, Zuzana; Dingemanse, Jasper

    2014-12-01

    Chemoattractant receptor-homologous molecule expressed on T helper (Th) 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key mediator in inflammatory disorders such as asthma and allergic rhinitis. In this study, we investigated the single- and multiple-dose tolerability and pharmacokinetics (PKs) of setipiprant, an orally active, potent, and selective CRTH2 antagonist. This randomized, double-blind, placebo-controlled study was performed in two parts in healthy male subjects. In study Part A, single oral doses of up to 2000 mg setipiprant or placebo were given to sequential groups of eight subjects each. Additionally, the impact of food on the PKs was investigated in one-dose group. In study Part B, two groups of subjects received 500 or 1000 mg setipiprant or placebo b.i.d. during 5.5 days. At regular intervals, tolerability variables and plasma and urine levels of setipiprant were determined. Setipiprant was well tolerated after single- and multiple-dose administration. Headache was the most frequently reported adverse event. No treatment effect on tolerability variables was observed. After single- and multiple-dose administration, setipiprant was rapidly absorbed and followed a biphasic elimination pattern with an elimination half-life between 10 and 18 h. Steady-state conditions were reached after 2-3 days and setipiprant did not accumulate. Exposure to setipiprant was lower in the presence of food. Urinary excretion of unchanged setipiprant did not exceed 7% of the administered dose. In this entry-into-human study, setipiprant showed good tolerability and a favorable PK profile, thus warranting its development in the treatment of inflammatory disorders. PMID:24734908

  16. A SINGLE HIGH DOSE OF METHAMPHETAMINE INCREASES COCAINE SELF-ADMINISTRATION BY DEPLETION OF STRIATAL DOPAMINE IN RATS

    PubMed Central

    XI, Z.-X.; KLEITZ, H. K.; DENG, X.; LADENHEIM, B.; PENG, X.-Q.; LI, X.; GARDNER, E. L.; STEIN, E. A.; CADET, J. L.

    2013-01-01

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10–20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kg×1 or 10 mg/kg/2 h×4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in “breakpoint” levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10–20 mg/kg) produced large DA release (4000%–6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  17. Patient-Specific Quality Assurance for Prostate Cancer Patients Receiving Spot Scanning Proton Therapy Using Single-Field Uniform Dose

    SciTech Connect

    Zhu, X. Ronald; Poenisch, Falk; Song, Xiaofei; Johnson, Jennifer L.; Ciangaru, George; Taylor, M. Brad; Lii, Ming Fwu; Martin, Craig; Arjomandy, Bijan; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh nhu; Gillin, Michael T.; Sahoo, Narayan

    2011-10-01

    Purpose: To describe our experiences with patient-specific quality assurance (QA) for patients with prostate cancer receiving spot scanning proton therapy (SSPT) using single-field uniform dose (SFUD). Methods and Materials: The first group of 249 patients with prostate cancer treated with SSPT using SFUD was included in this work. The scanning-beam planning target volume and number of monitor units were recorded and checked for consistency. Patient-specific dosimetric measurements were performed, including the point dose for each plan, depth doses, and two-dimensional (2D) dose distribution in the planes perpendicular to the incident beam direction for each field at multiple depths. The {gamma}-index with 3% dose or 3-mm distance agreement criteria was used to evaluate the 2D dose distributions. Results: We observed a linear relationship between the number of monitor units and scanning-beam planning target volume. The difference between the measured and calculated point doses (mean {+-} SD) was 0.0% {+-} 0.7% (range, -2.9% to 1.8%). In general, the depth doses exhibited good agreement except at the distal end of the spread-out Bragg peak. The pass rate of {gamma}-index (mean {+-} SD) for 2D dose comparison was 96.2% {+-} 2.6% (range, 90-100%). Discrepancies between the measured and calculated dose distributions primarily resulted from the limitation of the model used by the treatment planning system. Conclusions: We have established a patient-specific QA program for prostate cancer patients receiving SSPT using SFUD.

  18. A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats.

    PubMed

    Xi, Z-X; Kleitz, H K; Deng, X; Ladenheim, B; Peng, X-Q; Li, X; Gardner, E L; Stein, E A; Cadet, J L

    2009-06-30

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10-20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kgx1 or 10 mg/kg/2 hx4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in "break-point" levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10-20 mg/kg) produced large DA release (4000%-6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  19. A novel CRTH2 antagonist: Single- and multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-453859 in healthy subjects.

    PubMed

    Géhin, Martine; Strasser, Daniel S; Zisowsky, Jochen; Farine, Hervé; Groenen, Peter M A; Dingemanse, Jasper; Sidharta, Patricia N

    2015-07-01

    The chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 , a key mediator in inflammatory disorders. In this randomized, double-blind, placebo-controlled study we investigated the single- and multiple-dose tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) up to a dose of 800 mg once a day of ACT-453859, a potent and selective CRTH2 antagonist. ACT-453859 was moderately rapidly absorbed and followed a biphasic elimination pattern, with an elimination half-life between 11 and 20 hours. Steady-state conditions were reached after 1 day, and ACT-453859 did not accumulate. Urinary excretion of unchanged ACT-453859 did not exceed 1.4% of the administered dose. Administration of ACT-453859 resulted in a dose-dependent blockadeof CRTH2 on the surface of eosinophils. The maximum PD effect of ACT-453859 was reached about 2.0 hours after dosing, which corresponded to the highest concentration at which PD were assessed. At steady state, 100 and 800 mg ACT-453859 once a day resulted in blockade of CRTH2 over 24 hours. In this entry-into-humans study, ACT-453859 showed good tolerability at all doses and a PK and PD profile compatible with once-daily dosing. PMID:25655470

  20. Single-dose safety, tolerability, and pharmacokinetics of the antibiotic GSK1322322, a novel peptide deformylase inhibitor.

    PubMed

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

    2013-05-01

    GSK1322322 is a potent inhibitor of peptide deformylase, an essential bacterial enzyme required for protein maturation. GSK1322322 is active against community-acquired skin and respiratory tract pathogens, including methicillin-resistant Staphylococcus aureus, multidrug-resistant Streptococcus pneumoniae, and atypical pathogens. This phase I, randomized, double-blind, placebo-controlled, 2-part, single-dose, dose escalation study (first time in humans) evaluated the safety, tolerability, and pharmacokinetics of GSK1322322 (powder-in-bottle formulation) in healthy volunteers. In part A, dose escalation included GSK1322322 doses of 100, 200, 400, 800, and 1,500 mg under fasting conditions and 800 mg administered with a high-fat meal. In part B, higher doses of GSK1322322 (2,000, 3,000, and 4,000 mg) were evaluated under fasting conditions. Of the 39 volunteers enrolled in the study, 29 and 10 volunteers were treated with GSK1322322 and placebo, respectively. Upon single-dose administration, GSK1322322 was absorbed rapidly, with median times to maximum plasma concentration (T(max)) ranging from 0.5 to 1.0 h. The maximum observed plasma concentration (C(max)) and exposure (area under the concentration-time curve [AUC]) of GSK1322322 were greater than dose proportional between 100 and 1,500 mg and less than dose proportional between 1,500 and 4,000 mg. Administration of the drug with a high-fat meal reduced the rate of absorption (reduced C(max) and delayed T(max)) without affecting the extent of absorption (no effect on AUC). GSK1322322 was generally well tolerated, with all adverse events being mild to moderate in intensity during both parts of the study. The most frequently reported adverse event was headache. Data from this study support further evaluation of GSK1322322. PMID:23403431

  1. Single-dose gentamicin clearance is a predictor of creatinine clearance in spinal man.

    PubMed

    Segal, Jack L; Gilman, Thomas A; Thompson, John F

    2010-01-01

    To identify a radionuclide-free, SCI (spinal cord injury) population-specific method for estimating renal function utilizing the total body clearance of gentamicin as a measure of creatinine clearance (CL(cr)) and glomerular filtration rate (GFR). To incorporate SCI population-specific patient variables into a predictive model for estimating CLcr and GFR. A retrolective study of gentamicin clearance as a measure of GFR in patients with SCI. Each patient had received a single, intravenous dose of gentamicin. Simultaneously, a 24-hour creatinine clearance (CL(cr-24)) was obtained. Experimentally measured total body clearance of a single intravenous administration of gentamicin (CL(gent-iv)) was estimated from PK analyses of gentamicin disposition in patients with SCI. Comparisons were made between CL(gent-iv) and predictors of GFR derived from a SCI population-specific nomogram (SCI-psn), the method of Cockcroft and Gault (C-G), CL(cr-24), and a multiplicative statistical model. A multiplicative model, calculated gentamicin clearance (CL(gent-calc)), that incorporates SCI population-specific characteristics to predict CL(cr-24) and GFR was derived from a multivariate nonlinear regression analysis, and the strengths of association between CL(gent-iv) and CL(gent-calc), and estimates of GFR derived from the method of C-G, SCI-psn, and CL(cr-24) were tested. The best predictive performance was demonstrated for CL(gent-iv) and the multiplicative model, CL(gent-calc), when tested against CL(cr-24) or the SCI-psn, supporting our premise that CL(gent-iv) can be used to estimate GFR in SCI. CL(gent-iv) and CL(gent-calc) outperformed CL(cr-24), the method of C-G, and the SCI-psn as predictors of GFR. The multiplicative model produced estimates of CL(gent-iv) which were more precise and less biased than CL(cr-24), the standard radiation-free predictor of GFR in patients with SCI, the SCI-psn, and the C-G equation. In this preliminary study, the clearance of gentamicin

  2. Prediction of maintenance dose required to attain a desired drug concentration at steady-state from a single determination of concentration after an initial dose.

    PubMed

    Slattery, J T; Gibaldi, M; Koup, J R

    1980-01-01

    Strong correlations have been reported between drug concentrations at steady-state and a single drug concentration determined sometime after an initial dose for lithium, nortriptyline, imipramine, desipramine, choramphenicol and theophylline. The mathematical basis of these relationships suggests that a one point method for predicting steady-state drug concentrations and individual dosing requirements should be widely applicable to most drugs and should be valid for patients having a wide range of drug half-lives. A method is presented for evaluating the optimum time of blood sampling to determine a drug concentration in serum of plasma that best correlates with steady-state levels and for defining the range of drug half-lives beyond which the predictive approach is likely to give poor results. PMID:7398172

  3. Deposition of 7-aminoflunitrazepam and flunitrazepam in hair after a single dose of Rohypnol.

    PubMed

    Negrusz, A; Moore, C M; Hinkel, K B; Stockham, T L; Verma, M; Strong, M J; Janicak, P G

    2001-09-01

    In recent years, there has been a notable increase in the number of reports on drug-facilitated sexual assault. Benzodiazepines are the most common so-called "date-rape" drugs, with flunitrazepam (Rohypnol) being one of the most frequently mentioned. The aim of this study was to determine whether flunitrazepam and its major metabolite 7-aminoflunitrazepam could be detected in hair collected from ten healthy volunteers after receiving a single 2 mg dose of Rohypnol using solid phase extraction and NCI-GC-MS. Such data would be of great importance to law enforcement agencies trying to determine the best time interval for hair collection from a victim of drug-facilitated sexual assault in order to reveal drug use. Ten healthy volunteers (eight women and two men, 21 to 49 years old) participated in the study. The following hair samples were collected from each volunteer: one before flunitrazepam administration, and 1, 3, 5, 14, 21, and 28 days after. In five volunteers, 7-aminoflunitrazepam was detected 24 h after flunitrazepam administration and remained in hair throughout the entire 28-day study period (0.6-8.0 pg/mg). In two cases, 7-aminoflunitrazepam appeared in hair 21 days after drug intake (0.5-2.7 pg/mg), and in two subjects 14 days later (0.5-5.4 pg/mg). In one volunteer, 7-aminoflunitrazepam was detected on day 14 and 21 but concentrations were below the quantitation limit. Flunitrazepam was detected in some samples but all concentrations were below the quantitation limit (0.5-2.3 pg/mg). PMID:11569557

  4. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    PubMed

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials. PMID:26650973

  5. The effects of a single dose of concentrated beetroot juice on performance in trained flatwater kayakers.

    PubMed

    Muggeridge, David J; Howe, Christopher C F; Spendiff, Owen; Pedlar, Charles; James, Philip E; Easton, Chris

    2013-10-01

    The aim of the current study was to determine the effects of dietary nitrate ingestion on parameters of submaximal and supramaximal exercise and time trial (TT) performance in trained kayakers. Eight male kayakers completed four exercise trials consisting of an initial discontinuous graded exercise test to exhaustion and three performance trials using a kayak ergometer. The performance trials were composed of 15 min of paddling at 60% of maximum work rate, five 10-s all-out sprints, and a 1 km TT. The second and third trials were preceded by ingestion of either 70 ml nitrate-rich concentrated beetroot juice (BR) or tomato juice (placebo [PLA]) 3 hr before exercise using a randomized crossover design. Plasma nitrate (PLA: 33.8 ± 1.9 μM, BR: 152 ± 3.5 μM) and nitrite (PLA: 519.8 ± 25.8, BR: 687.9 ± 20 nM) were higher following ingestion of BR compared with PLA (both p < .001). VO2 during steady-state exercise was lower in the BR trial than in the PLA trial (p = .010). There was no difference in either peak power in the sprints (p = .590) or TT performance between conditions (PLA: 277 ± 5 s, BR: 276 ± 5 s, p = .539). Despite a reduction in VO2, BR ingestion appears to have no effect on repeated supramaximal sprint or 1 km TT kayaking performance. A smaller elevation in plasma nitrite following a single dose of nitrate and the individual variability in this response may partly account for these findings. PMID:23580456

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

    PubMed

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

    2016-04-01

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

  7. A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

    PubMed Central

    Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

    2011-01-01

    Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

  8. A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes.

    PubMed

    Sacks, S L; Shafran, S D; Diaz-Mitoma, F; Trottier, S; Sibbald, R G; Hughes, A; Safrin, S; Rudy, J; McGuire, B; Jaffe, H S

    1998-11-01

    A randomized, double-blind, clinic-initiated, sequential dose-escalation pilot study was performed to compare the safety and efficacy of single applications of 1, 3, and 5% cidofovir gel with placebo in the treatment of early, lesional, recurrent genital herpes at five Canadian outpatient sites. Ninety-six patients began treatment within 12 h of lesion appearance and were evaluated twice daily until healing of the lesion occurred. Cidofovir gel at all strengths significantly decreased the median time to negative virus culture in a dose-dependent fashion (3.0 days in the placebo group versus 2.2, 1.3, and 1.1 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively; P = 0.02, 0.0001, and 0.0003, respectively). A trend toward a reduction in the median time to complete healing in association with treatment was present, but the differences were not statistically significant (5.0 days in the placebo group versus 4.3, 4.1, and 4.6 days in the 1, 3, and 5% cidofovir gel treatment groups, respectively). Application site reactions occurred in 3, 5, 19, and 22% of the patients in these four groups, respectively. Treatment-associated lesion recrudescence with delayed healing, which is suggestive of local toxicity, was observed in three patients treated with 5% cidofovir gel and one patient treated with 3% cidofovir gel. In summary, single-dose application of cidofovir gel confers a significant antiviral effect on lesions of recurrent genital herpes. Additional studies are warranted to further identify the optimal efficacious dose of cidofovir in association with the maximum gel strength that can be tolerated. PMID:9797239

  9. The Biological Effect of Large Single Doses: A Possible Role for Non-Targeted Effects in Cell Inactivation

    PubMed Central

    Wenz, Frederik; Herskind, Carsten

    2014-01-01

    Background and Purpose Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. Material and Methods Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM). Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. Results The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4–16.3; P<0.0001) when the density of irradiated cells was increased from 10 to 50×103 cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5–15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1–12 h. Conclusions A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5–15 Gy. The dependence of SF on cell numbers at high doses would represent a “cohort effect” in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy. PMID:24465461

  10. The effects of colesevelam HCl on the single-dose pharmacokinetics of glimepiride, extended-release glipizide, and olmesartan medoxomil.

    PubMed

    He, Ling; Wickremasingha, Prachi; Lee, James; Tao, Ben; Mendell-Harary, Jeanne; Walker, Joseph; Wight, Douglas

    2014-01-01

    Bile acid sequestrants can potentially bind to concomitant drugs. Single-dose studies evaluated the effects of colesevelam on the pharmacokinetics of glimepiride, glipizide extended-release (ER), and olmesartan medoxomil. Each study enrolled healthy subjects aged 18-45 years. The olmesartan medoxomil study used a randomized adaptive crossover design that initially compared olmesartan medoxomil alone versus simultaneously with colesevelam, then olmesartan medoxomil alone versus 4 hours before colesevelam. The other studies used a three-period crossover design (test drug alone, test drug simultaneously with colesevelam, and test drug 4 hours before colesevelam). For the colesevelam coadministration periods, 3,750 mg once daily was dosed throughout the pharmacokinetic sampling period. After each single dose of test drug, serial blood samples were collected for determination of plasma drug concentrations and calculation of pharmacokinetic parameters. Administering colesevelam simultaneously with glimepiride or glipizide ER resulted in minor reductions (18% and 13%, respectively) in total exposure that were negated by staggering colesevelam dosing by 4 hours. Administering colesevelam simultaneously with olmesartan medoxomil resulted in a major reduction (39%) in olmesartan exposure that was reduced by staggering colesevelam dosing by 4 hours. This reduction in olmesartan exposure is not predicted to have a clinically significant impact on blood pressure control. PMID:24019110

  11. Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience

    PubMed Central

    LY, K. INA; CREW, LAURA L.; GRAHAM, CARRIE A.; MRUGALA, MACIEJ M.

    2016-01-01

    Rituximab (RTX) improves the outcome in patients with systemic diffuse large B-cell lymphoma (DLBCL), but its benefit in primary central nervous system lymphoma (PCNSL) is unclear. In the present study, a single-institution retrospective analysis was performed for 12 patients with newly diagnosed PCNSL treated with combined high-dose methotrexate (HD-MTX) and RTX. MTX was administered biweekly at 8 g/m2/dose until a complete response (CR) was achieved or for a maximum of eight doses. RTX was provided for a total of eight weekly doses at 375 mg/m2/dose. Following a median of 11 cycles of MTX, the radiographic overall response rate was 91% and the CR rate was 58%. A CR was achieved after a median 6 cycles of MTX. The median progression-free survival time was 22 months and the median overall survival time has not yet been attained. These results compare favorably to single-agent HD-MTX and suggest a role for immunochemotherapy in the treatment of PCNSL. PMID:27123138

  12. Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers.

    PubMed Central

    Nakashima, M; Uematsu, T; Kosuge, K; Umemura, K; Hakusui, H; Tanaka, M

    1995-01-01

    The pharmacokinetics and tolerance of DU-6859a, 7-[(7S)-7-amino-5-azaspiro[2,4]heptan-5-yl]-8-chloro-6-fluor o-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid sesquihydrate, were investigated in healthy male Japanese volunteers after single (25, 50, 100, and 200 mg) and multiple (100 mg three times a day for 6 days plus once a day on the 7th day and 50 mg every 12 h for 13 doses) oral doses. DU-6859a was well tolerated at all doses, and all 36 subjects completed the study; mild transient soft stool in five volunteers and mild transient diarrhea in one volunteer on the multiple-dose (100 mg three times a day) study were the only side effects reported. No drug crystals were observed in the urine after the single 200-mg dose and the 100-mg three times a day regimen. DU-6859a was rapidly absorbed in the fasted state. The mean maximum concentration in serum (Cmax) ranged from 0.29 to 1.86 micrograms/ml for the 25- to 200-mg dose, and the mean time to reach Cmax ranged from 1.0 to 1.3 h. The terminal half-life ranged from 4.4 to 5.0 h. The area under the curve increased dose dependently. The serum protein binding of the drug was approximately 50%. The apparent volume of distribution clearly exceeded 1 liter/kg, suggesting good tissue penetration. Within 48 h, the cumulative urinary recovery of unchanged drug amounted to 69 to 74% of the dose administered, while fecal excretion up to 48 h after the 200-mg dose accounted for ca. 3% of the dose. Food intake did not affect the rate and extend of absorption of DU-6859a to a clinically significant extent. During multiple oral dosing, the accumulation of the drug in serum was close to the theoretically predicted values, which indicated that there was virtually no drug accumulation. PMID:7695301

  13. Single- and Repeated-Dose Pharmacokinetics of Ceftaroline in Plasma and Soft Tissues of Healthy Volunteers for Two Different Dosing Regimens of Ceftaroline Fosamil.

    PubMed

    Matzneller, Peter; Lackner, Edith; Lagler, Heimo; Wulkersdorfer, Beatrix; Österreicher, Zoe; Zeitlinger, Markus

    2016-06-01

    Ceftaroline fosamil (CPT-F) is currently approved for use for the treatment of complicated skin and soft tissue infections and community-acquired pneumonia at 600 mg twice daily (q12h), but other dosing regimens are under evaluation. To date, very limited data on the soft tissue pharmacokinetics (PK) of the active compound, ceftaroline (CPT), are available. CPT concentrations in the plasma, muscle, and subcutis of 12 male healthy volunteers were measured by microdialysis after single and repeated intravenous administration of 600 mg CPT-F q12h or three times daily (q8h) in two groups of 6 subjects each. Relevant PK and PK/pharmacodynamic (PD) parameters were calculated and compared between groups. In plasma, the area under the concentration-time curve (AUC) from 0 to 24 h for total CPT and the cumulative percentage of the dosing interval during which the free drug concentrations exceeded the MIC (fTMIC) for unbound CPT for the currently established threshold of 1 mg/liter were significantly higher in the group receiving CPT-F q8h. Exposure to free drug in soft tissues was higher in the group receiving CPT-F q8h, but high interindividual variability in relevant PK parameters was observed. The mean ratios of the AUC from time zero to the end of the dosing interval (AUC0-τ) for free CPT in soft tissues and the AUC0-τ for the calculated free fraction in plasma at steady state ranged from 0.66 to 0.75. Administration of CPT-F q8h led to higher levels of drug exposure in all investigated compartments. When MIC values above 1 mg/liter were assumed, the calculated fTMIC after dosing q12h was markedly lower than that after dosing q8h. The clinical implications of these differences are discussed in light of recently completed clinical phase III and PK/PD studies. PMID:27044549

  14. Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

    PubMed

    Gårevik, N; Börjesson, A; Choong, E; Ekström, L; Lehtihet, M

    2016-06-01

    The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated. PMID:26370185

  15. Comparative metabolism studies of hexabromocyclododecane (HBCD) diastereomers in male rats following a single oral dose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively 42% of dose for alpha-HBCD,...

  16. High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

    SciTech Connect

    Yamada, Yoshiya Bilsky, Mark H.; Lovelock, D. Michael; Venkatraman, Ennapadam S.; Toner, Sean; Johnson, Jared; Zatcky, Joan N.P.; Zelefsky, Michael J.; Fuks, Zvi

    2008-06-01

    Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

  17. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    PubMed Central

    Barry, B; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C

    1996-01-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media. PMID:8878566

  18. Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects

    PubMed Central

    2014-01-01

    Background Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis and cell-mediated immunity. Based on these hematopoietic and immunomodulatory activities, a recombinant human IL-12 (rHuIL-12) is now under development to address the unmet need for a medical countermeasure against the hematopoietic syndrome of the acute radiation syndrome (HSARS) that occurs in individuals exposed to lethal radiation, and also to serve as adjuvant therapy that could provide dual hematopoietic and immunotherapeutic benefits in patients with cancer receiving chemotherapy. We sought to demonstrate in healthy subjects the safety of rHuIL-12 at single, low doses that are appropriate for use as a medical countermeasure for humans exposed to lethal radiation and as an immunomodulatory anti-cancer agent. Methods Two placebo-controlled, double-blinded studies assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL-12. The first-in-human (FIH) dose-escalation study randomized subjects to single subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 μg doses. Due to toxicity, dose was reduced to 15 μg and then to 12 μg. The phase 1b expansion study randomized subjects to the highest safe and well tolerated dose of 12 μg. Results Thirty-two subjects were enrolled in the FIH study: 4 active and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 μg; 1 active and 1 placebo at 20 μg. Sixty subjects were enrolled in the expansion study: 48 active and 12 placebo at 12 μg dose of rHuIL-12. In both studies, the most common adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting significant distribution into extravascular spaces. rHuIL-12 triggered transient changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer cells, and CD34+ hematopoietic progenitor cells, and induced increases in interferon-γ and C-X-C motif

  19. Efficacy of single-dose dexamethasone implantation in patients with persistent diabetic macular edema.

    PubMed

    Arıkan Yorgun, Mücella; Toklu, Yasin; Mutlu, Melek; Uysal, Betül Seher; Çakmak, Hasan Basri

    2016-08-01

    To investigate the efficacy of single-dose intravitreal dexamethasone implantation in the treatment of persistent diabetic macular edema (DME) unresponsive to 3 consecutive ranibizumab injections over a period of 6 months. Forty-one patients with a previous history of treatment for DME including at least three consecutive intravitreal ranibizumab injections were enrolled in this retrospective study. Main outcome measures were change in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure from baseline to 6th month. At the baseline, the mean CMT was 572.4 ± 123.1 μm which improved to 264.2 ± 114.4, 317.7 ± 141.7, 410.6 ± 169.1, and 382.8 ± 181.5 μm at the 1st, 3rd, 5th, and 6th month, respectively (p < 0.05). The preoperative mean BCVA was 0.85 ± 0.54 logMAR units which improved to 0.76 ± 0.5 (p = 0.08), 0.69 ± 0.4 (p = 0.02), 0.74 ± 0.4 (p = 0.284), and 0.72 ± 0.3 (p = 0.489) logMAR units at the 1st, 3rd, 5th, and 6th months, respectively. Additional injections were required for 13 (31 %) eyes at 3rd month and 14 (34 %) eyes at 5th month due to recurrence of macular edema. Intravitreal dexamethasone implantation caused a significant improvement of BCVA and reduction of CMT in the patients with persistent DME that were unresponsive to 3 consecutive ranibizumab injections. However, retreatment before 6 months in the majority of the patients was needed despite the beneficial effects after the index procedure. PMID:26644130

  20. Single Oral Dose Pharmacokinetics of Decursin and Decursinol Angelate in Healthy Adult Men and Women

    PubMed Central

    Zhang, Jinhui; Li, Li; Hale, Thomas W.; Chee, Wayne; Xing, Chengguo; Jiang, Cheng; Lü, Junxuan

    2015-01-01

    The ethanol extract of Angelica gigas Nakai (AGN) root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D) and decursinol angelate (DA) contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH) in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY) in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax) of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax) of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2) for D and DA was similar (17.4 and 19.3 h) and each was much longer than that of DOH (7.4 h). The mean area under the curve (AUC0-48h) for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation. Trial Registration ClinicalTrials.gov NCT02114957 PMID:25695490

  1. Activity of the human carcinogens benzidine and 2-naphthylamine in triple- and single-dose mouse bone marrow micronucleus assays: results for a combined test protocol.

    PubMed

    Mirkova, E

    1990-01-01

    The activities of the human bladder carcinogens benzidine and 2-naphthylamine in the mouse bone marrow micronucleus assays using a limited test protocol (oral dosing to male mice, sampling 24 h later) have recently been established. As a contribution to the International Collaborative Study on the evaluation of the sensitivity of the triple-dose micronucleus test protocol it was decided to re-evaluate benzidine and 2-naphthylamine using a combined triple- and single-dose test protocol. Benzidine gave a clear positive response in male mice 24 h after 3 daily doses of 150 and 300 mg/kg. A single dose of 900 mg/kg of benzidine gave a weaker response 24 h after dosing. In the case of 2-naphthylamine a stronger positive response was observed 24 h after a single dose of 600 mg/kg as compared to 3 daily doses of 200 or 400 mg/kg. There was no significant difference in the increased positive response observed for a single dose of 30 mg/kg of cyclophosphamide compared with 3 successive daily doses of 10 mg/kg. Based on the present data the combined triple/single-dose micronucleus test protocol is strongly supported. PMID:2366784

  2. Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

    PubMed

    Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

    2016-09-01

    An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole. PMID:27372549

  3. Radial Dose Profiles: Calculation Refinements and Sensitivities to Single Event Effects Analysis

    NASA Technical Reports Server (NTRS)

    Patterson, Jeffrey; Swimm, Randall

    2005-01-01

    Comparisons of radial dose calculation are performed, as well as the introduction of important physics to improve the calculation techniques. Also, the consequences to device performance are explored via numerical simulations.

  4. EFFECT OF SINGLE VERSUS SPLIT DOSES OF DIETHYINITROSAMINE ON THE INDUCTION OF GAMMA-GLUTAMYLTRANSPEPTIDASE-FOCI IN THE LIVERS OF ADULT AND JUVENILE RATS

    EPA Science Inventory

    The induction of gamma-glutamyltranspeptidase (GGT)-foci by single and by split doses of diethylnitrosamine (DENA) was evaluated in the livers of juvenile and young adult male, Sprague-Dawley rats. A single dose of DENA was administered at either 32, 41 or 52 days of age and foll...

  5. OSL and TL techniques combined in a beryllium oxide detector to evaluate simultaneously accumulated and single doses.

    PubMed

    Malthez, Anna L M C; Freitas, Marcelo B; Yoshimura, Elisabeth M; Umisedo, Nancy K; Button, Vera L S N

    2016-04-01

    Optically stimulated luminescence (OSL) and thermoluminescence (TL) are similar techniques widely used in radiation dosimetry. The main difference between these techniques is the stimulus to induce luminescence emission: TL technique uses thermal stimulation, whereas OSL uses optical stimulation. One of the main intrinsic characteristics of the OSL technique is the possibility of reading several times the dosimetric materials with a negligible loss of signal. In the case of BeO, recent studies have shown that TL stimulation up to 250°C does not affect its OSL signal. Taking the advantages of dosimetric characteristics of BeO combined with both techniques, in this study, we demonstrated the possibility of measuring accumulated and single doses in the same BeO-based detector in order to use it to improve individual monitoring of radiation workers exposed to X-ray or gamma-ray fields. Single doses were measured using TL technique by heating the detector up to 250°C, whereas accumulated doses were estimated using OSL technique in the same detector in a relatively short time of optical stimulation. The detectors were exposed to two energies: 28keV X-rays and 1.25MeV Co-60 gamma rays. The doses estimated by OSL and TL of BeO (Thermalox 995) were compared with those obtained with LiF (TLD-100) and recorded with a calibrated ionization chamber. The results indicate that combined OSL and TL signals of BeO detectors can provide additional information of accumulated dose, with additional exploration of the advantages of both techniques, such as speed in readouts with OSL, and double-check the doses using TL and OSL intensities from BeO. PMID:26784853

  6. H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection

    PubMed Central

    Liang, Minmin; Fan, Kelong; Zhou, Meng; Duan, Demin; Zheng, Jiyan; Yang, Dongling; Feng, Jing; Yan, Xiyun

    2014-01-01

    An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox-loaded HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration than free Dox and significantly inhibited tumor growth after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery. PMID:25267615

  7. Single 1 g dose of cefotaxime in the treatment of infections due to penicillinase-producing strains of Neisseria gonorrhoeae.

    PubMed Central

    de Koning, G A; Tio, D; van den Hoek, J A; van Klingeren, B

    1983-01-01

    One hundred and two patients with an uncomplicated infection due to penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) were treated with a single 1 g dose of cefotaxime. At follow-up within 15 days all genital and rectal infections were cured. Pharyngeal infections also seemed to respond to this treatment. A relatively high proportion (30.9%) of patients, however, developed post-gonococcal urethritis. PMID:6299449

  8. Single immunizing dose of recombinant adenovirus efficiently induces CD8+ T cell-mediated protective immunity against malaria.

    PubMed

    Rodrigues, E G; Zavala, F; Eichinger, D; Wilson, J M; Tsuji, M

    1997-02-01

    The immunogenicity of a recombinant replication defective adenovirus expressing a major malaria Ag, the circumsporozoite (CS) protein (AdPyCS), was determined using a rodent malaria model. A single immunizing dose of this construct induced a large number of CS-specific CD8+ and CD4+ T cells in the spleens of these animals, particularly when given by the s.c. or i.m. route. A single dose of AdPyCS also induced high titers of Abs to Plasmodium yoelii sporozoites in mice. No other form of presentation of the CS protein given as a single immunizing dose, i.e., irradiated sporozoites, recombinant vaccinia, or influenza virus, etc., elicits comparably high numbers of CS-specific CD8+ T cells. The high concentration of CS-specific CD8+ T cells in the spleen was relatively short-lived, decreasing to half of its original value by 4 wk and to one-third at 8 wk after AdPyCS inoculation. The decrease in splenic CS-specific CD4+ T cells was even more rapid. Most importantly, a single dose of inoculation of AdPyCS into mice rendered them highly resistant to sporozoite challenge, resulting in a 93% inhibition of liver stage development of the parasites. This protective effect was primarily mediated by CD8+ T cells, as shown by depletion of this T cell population, while depletion of the CD4+ T cell population had only a minor effect on anti-plasmodial activity. Moreover, the inoculation of mice with AdPyCS induces sterile immunity in a significant proportion of mice, preventing the occurrence of parasitemia. PMID:9013969

  9. Regularities of Changes in the Properties of Silicon Single Crystals under Low-Dose Beta-Irradiation

    NASA Astrophysics Data System (ADS)

    Dmitrievskiy, A. A.

    2013-12-01

    Regularities of changes in the mechanical properties (micro- or nanohardness, fracture toughness at indentation, and steady-state creep rate) and electrical characteristics (Hall constant, conductivity, and concentration of electrically active defects) of silicon single crystals under low-dose ( F < 1012 cm-2) low-intensity ( I ~ 106 cm-2•s-1) beta-irradiation are described. The mechanism of nonmonotonic beta-induced softening of silicon is discussed.

  10. Evaluation of Oxfendazole, Praziquantel and Albendazole against Cystic Echinococcosis: A Randomized Clinical Trial in Naturally Infected Sheep

    PubMed Central

    Gavidia, Cesar M.; Gonzalez, Armando E.; Barron, Eduardo A.; Ninaquispe, Berenice; Llamosas, Monica; Verastegui, Manuela R.; Robinson, Colin; Gilman, Robert H.

    2010-01-01

    Background Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep. Methodology/Principal Findings A randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. “Noninfective” sheep were those that had no viable PSCs; “low-medium infective” were those that had 1% to 60% PSC viability; and “high infective” were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either “noninfective” or “low-medium infective” sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% “noninfective” or “low-medium infective” for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05). Conclusions/Significance We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are

  11. Peripheral doses in patients undergoing Cyberknife treatment for intracranial lesions. A single centre experience

    PubMed Central

    2011-01-01

    Background Stereotactic radiosurgery/radiotherapy procedures are known to deliver a very high dose per fraction, and thus, the corresponding peripheral dose could be a limiting factor for the long term surviving patients. The aim of this clinical study was to measure the peripheral dose delivered to patients undergoing intracranial Cyberknife treatment, using the MOSFET dosimeters. The influence of the supplemental shielding, the number of monitor units and the collimator size to the peripheral dose were investigated. Methods MOSFET dosimeters were placed in preselected anatomical regions of the patient undergoing Cyberknife treatment, namely the thyroid gland, the nipple, the umbilicus and the pubic symphysis. Results The mean peripheral doses before the supplemental shielding was added to the Cyberknife unit were 51.79 cGy, 13.31 cGy and 10.07 cGy while after the shielding upgrade they were 38.40 cGy, 10.94 cGy, and 8.69 cGy, in the thyroid gland, the umbilicus and the pubic symphysis, respectively. The increase of the collimator size corresponds to an increase of the PD and becomes less significant at larger distances, indicating that at these distances the PD is predominate due to the head leakage and collimator scatter. Conclusion Weighting the effect of the number of monitor units and the collimator size can be effectively used during the optimization procedure in order to choose the most suitable treatment plan that will deliver the maximum dose to the tumor, while being compatible with the dose constraints for the surrounding organs at risk. Attention is required in defining the thyroid gland as a structure of avoidance in the treatment plan especially in patients with benign diseases. PMID:22082279

  12. Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination.

    PubMed

    Prchal, Lukáš; Podlipná, Radka; Lamka, Jiří; Dědková, Tereza; Skálová, Lenka; Vokřál, Ivan; Lecová, Lenka; Vaněk, Tomáš; Szotáková, Barbora

    2016-07-01

    Albendazole (ABZ), widely used benzimidazole anthelmintic, administered to animals enters via excrements into environment and may impact non-target organisms. Moreover, exposure of lower development stages of helminths to anthelmintics may also encourage the development of drug-resistant strains of helminths. In present project, the kinetics of ABZ (10 mg kg(-1) p.o.) and its metabolite (ABZ.SO, ABZSO2) elimination in faeces from treated Texel lambs were studied using UHPLC/MS/MS with the aim to find out their concentrations achievable in the environment. Consequently, the effect of these compounds on lower development stages of Barber's pole worm (Haemonchus contortus) and on germination of white mustard (Sinapis alba) seeds was evaluated. The results showed that ABZ concentrations in faeces excreted in 4-60 h after treatment were above the concentrations lethal for H. contortus eggs. Moreover, pre-incubation with sub-lethal doses of ABZ and ABZ.SO did not increase the resistance of H. contortus eggs and larvae to anthelmintics. On the other hand, concentrations of ABZ and ABZ.SO in faeces are so high that might have negative influence on non-target soil invertebrates. As neither ABZ nor its metabolites affect the germination of mustard seeds, phytoremediation could be considered as potential tool for detoxification of ABZ in the environment. PMID:26996913

  13. Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal.

    PubMed

    West, K P; Khatry, S K; LeClerq, S C; Adhikari, R; See, L; Katz, J; Shrestha, S R; Pradhan, E K; Pokhrel, R P; Sommer, A

    1992-01-01

    A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects. PMID:1486669

  14. Pharmacokinetics of Single-Dose Dolutegravir in HIV-Seronegative Subjects With Moderate Hepatic Impairment Compared to Healthy Matched Controls

    PubMed Central

    Song, Ivy H; Borland, Julie; Savina, Paul M; Chen, Shuguang; Patel, Parul; Wajima, Toshihiro; Peppercorn, Amanda F; Piscitelli, Stephen C

    2013-01-01

    This study evaluated dolutegravir pharmacokinetics (PK) in subjects with moderate hepatic impairment compared to matched, healthy controls. In this open-label, parallel-group study, eight adult subjects with moderate hepatic impairment (Child-Pugh Score 7–9) and eight healthy subjects matched for gender, age, and body mass index received a single dolutegravir 50-mg dose. Following dosing, 72-hour PK sampling was performed to determine total and unbound dolutegravir concentrations. PK parameters were calculated using non-compartmental analysis. Geometric least squares mean ratios (GMR) and 90% confidence intervals (CIs) in subjects with hepatic impairment versus healthy subjects were generated by analysis of variance. Results showed that PK parameters of total plasma dolutegravir were similar between subject groups. The unbound fraction was higher in subjects with moderate hepatic impairment than in healthy subjects with GMR (90% CI) of 2.20 (1.62, 2.99) for unbound fraction at 3 hours post-dose and 1.76 (1.23, 2.51) for unbound fraction at 24 hours post-dose; this correlated with lower serum albumin concentrations and was not considered clinically significant. Dolutegravir was well tolerated in both groups; all adverse events were reported as minor. Although free fraction was increased, no dose adjustment is required for patients treated with dolutegravir who have mild to moderate hepatic impairment. PMID:26097786

  15. Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD.

    PubMed

    Brown, J T; Abdel-Rahman, S M; van Haandel, L; Gaedigk, A; Lin, Y S; Leeder, J S

    2016-06-01

    The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 μM*h in EM2s to 5.8 ± 1.7 μM*h, 16.3 ± 2.9 μM*h, and 50.2 ± 7.3 μM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication. PMID:26660002

  16. A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic.

    PubMed

    Oosterlinck, W; Philp, N H; Charig, C; Gillies, G; Hetherington, J W; Lloyd, J

    1990-04-01

    The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic. PMID:2341581

  17. A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

    PubMed

    Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

    2015-07-31

    Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. PMID:26144899

  18. Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial

    PubMed Central

    Gulec, Seza A.; Cohen, Steven J.; Pennington, Kenneth L.; Zuckier, Lionel S.; Hauke, Ralph J.; Horne, Heather; Wegener, William A.; Teoh, Nick; Gold, David V.; Sharkey, Robert M.; Goldenberg, David M.

    2014-01-01

    Purpose Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results 111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion 90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. PMID:21527562

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

    PubMed Central

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

    2015-01-01

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

  20. Single-dose antibiotic therapy: what has the past taught us?

    PubMed

    Carbón, C

    1992-08-01

    The proper dosage schedule of antibiotics has generally been determined empirically, due to the difficulty of clinical trials. Initially, the dosage was chosen to allow high sustained levels greater than MIC in the blood. Antibiotics (beta lactams, tetracyclins, macrolides) were given at high doses three to six times daily, whatever their kinetic properties. The data obtained by Eagle3 with beta lactams in animal models of streptococcal and treponemal infections outlined the importance of interval between doses on the in vivo efficacy. They also showed that increasing the dose of penicillin had a positive effect on the bactericidal activity only through the persistence of effective levels (greater than MIC) at the site of infection. Further illustrations were given through experimental and clinical studies with beta lactams or other compounds on different types of infections: LRTIs, UTIs, meningitis, and endocarditis. The importance of both dynamic (i.e., pattern of bactericidal effect) and kinetic (elimination half-life) parameters was thus further identified. Information on toxicity with some compounds with a narrow therapeutic index, such as aminoglycosides, indicated that increasing the dose to enhance efficacy had some limitations. This led to numerous studies on the relations between concentration and toxicity, stating that nephro- or ototoxicity were not directly related to peak level in serum. Experimental studies showed that OD administration of aminoglycosides was both more efficient and less toxic than the multiple-dose regimen of the same daily amount. Economic considerations progressively justified attempts to both reduce the dose and the work load related to multiple administrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1487556

  1. Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

    PubMed Central

    Kobylinski, Kevin C.; Alout, Haoues; Foy, Brian D.; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E.; Richardson, Jason H.

    2014-01-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  2. In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents.

    PubMed

    Cedillo-Rivera, R; Muñoz, O

    1992-09-01

    The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5-nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5-nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated. PMID:1518040

  3. Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control.

    PubMed

    Kobylinski, Kevin C; Alout, Haoues; Foy, Brian D; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E; Richardson, Jason H

    2014-10-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  4. Determination of albendazole sulfoxide in human plasma by using liquid chromatography-tandem mass spectrometry.

    PubMed

    Saraner, Nihal; Özkan, Güler Yağmur; Güney, Berrak; Alkan, Erkin; Burul-Bozkurt, Nihan; Sağlam, Onursal; Fikirdeşici, Ezgi; Yıldırım, Mevlüt

    2016-06-01

    A rapid, simple and sensitive method was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of albendazole sulfoxide (ABZOX) in human plasma. The plasma samples were extracted by protein precipitation using albendazole sulfoxide-d3 as internal standard (IS). The chromatographic separation was performed on Waters Xbridge C18Column (100×4.6mm, 3.5μm) with a mobile phase consisting of ammonia solution, water and methanol at a flow rate of 0.70mL/min. ABZOX was detected and identified by mass spectrometry with electrospray ionization (ESI) in positive ion and multiple-reaction monitoring (MRM) mode. The method was linear in the range of 3-1500ng/mL for ABZOX. This method was successfully applied to the bioequivalence study in human plasma samples. PMID:27060508

  5. Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study.

    PubMed

    Dariane, Charles; Amin, Alexandre; Lortholary, Olivier; Lalli, Alexandre; Michel, Constance; Le Guilchet, Thomas; Treluyer, Jean-Marc; Nguyen-Khoa, Thao; De Toma, Claudia; Urien, Saïk; Méjean, Arnaud; Bourget, Philippe; Timsit, Marc-Olivier

    2016-08-01

    The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P < 0.001); median intraprostatic concentrations were 16.6 mg/L (95% CI 13.3-31.4 mg/L) and 4.2 mg/L (95% CI 3.1-4.9 mg/L), respectively (P < 0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P = 0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials. PMID:27324263

  6. On the use of a single-fiber multipoint plastic scintillation detector for 192Ir high-dose-rate brachytherapy

    PubMed Central

    Therriault-Proulx, François; Beddar, Sam; Beaulieu, Luc

    2013-01-01

    Purpose: The goal of this study was to prove the feasibility of using a single-fiber multipoint plastic scintillation detector (mPSD) as an in vivo verification tool during 192Ir high-dose-rate brachytherapy treatments. Methods: A three-point detector was built and inserted inside a catheter-positioning template placed in a water phantom. A hyperspectral approach was implemented to discriminate the different optical signals composing the light output at the exit of the single collection optical fiber. The mPSD was tested with different source-to-detector positions, ranging from 1 to 5 cm radially and over 10.5 cm along the longitudinal axis of the detector, and with various integration times. Several strategies for improving the accuracy of the detector were investigated. The device's accuracy in detecting source position was also tested. Results: Good agreement with the expected doses was obtained for all of the scintillating elements, with average relative differences from the expected values of 3.4 ± 2.1%, 3.0 ± 0.7%, and 4.5 ± 1.0% for scintillating elements from the distal to the proximal. A dose threshold of 3 cGy improved the general accuracy of the detector. An integration time of 3 s offered a good trade-off between precision and temporal resolution. Finally, the mPSD measured the radioactive source positioning uncertainty to be no more than 0.32 ± 0.06 mm. The accuracy and precision of the detector were improved by a dose-weighted function combining the three measurement points and known details about the geometry of the detector construction. Conclusions: The use of a mPSD for high-dose-rate brachytherapy dosimetry is feasible. This detector shows great promise for development of in vivo applications for real-time verification of treatment delivery. PMID:23718599

  7. Miltefosine lipid nanocapsules: Intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni.

    PubMed

    El-Moslemany, Riham M; Eissa, Maha M; Ramadan, Alyaa A; El-Khordagui, Labiba K; El-Azzouni, Mervat Z

    2016-07-01

    A dual drug repurposing/nanotechnological approach was used to develop an alternative oral treatment for schistosomiasis mansoni using miltefosine (MFS), an anticancer alkylphosphocholine, and lipid nanocapsules (LNCs) as oral nanovectors. We demonstrated earlier that MFS possesses significant activity against different developmental stages of Schistosoma mansoni in the mouse model using 5 successive 20mg/kg/day oral doses. Moreover, an effective single dose (20mg/kg) oral treatment against the adult stage of S. mansoni in mice was developed using LNCs, particularly modified with CTAB, a positive charge imparting agent (MFS-LNC-CTAB(+)), or oleic acid as membrane permeabilizer (MFS-LNC-OA). Efficacy enhancement involved, at least in part, targeting of the worm tegument with MFS-LNCs as a new therapeutic entity. As the tegument surface charge and composition may differ in pre-patent stages of the parasite, it was of importance in the present study to assess the efficacy of a single oral dose of the two MFS-LNC formulations against invasive and immature stages for potential advantage relative to praziquantel. Results indicated potent schistosomicidal effects against both invasive and immature stages of S. mansoni in infected mice, efficacy being both formulation and developmental stage dependent. This was indicated by the significant reduction in the total worm burden of the invasive stage by 91.6% and 76.8% and the immature stage by 82.7% and 96.7% for MFS-LNC-CTAB+ and MFS-LNC-OA, respectively. Histopathological findings indicated amelioration of hepatic pathology with regression of the granulomatous inflammatory reaction and reduction in granulomas number and size, verifying marked improvement in architecture of hepatic lobules. From a clinical perspective, MFS-LNCs offer potential as an alternative single oral dose nanomedicine with a wide therapeutic profile for the mass chemotherapy of schistosomiasis mansoni. PMID:27039667

  8. Acute phase response in toxicity studies. I. Survey of beagle dogs subjected to single-dose toxicity studies.

    PubMed

    Hoshiya, T; Watanabe, D; Akagi, K; Mizoguchi, Y; Kamiya, K; Mizuguchi, H; Kumahara, M; Toya, H; Nagashima, Y; Okaniwa, A

    2001-05-01

    In the field of routine single-dose toxicity studies, we occasionally meet with transient leukocytosis associated with an increase in fibrinogen in beagle dogs within a few days after treatment with the test article. Only a little is known, however, about the toxicological significance of these changes. However, these changes were thought to belong to the category of "Acute Phase Response, APR," which has been known for a long time in connection with injury, trauma or infection. Aiming at proper understanding of these experiences, we surveyed 25 single-dose toxicity studies (7 intravenous bolus, 5 intravenous infusion, 12 oral and 1 subcutaneous treatment, hereafter referred to simply as i.v. bolus, i.v. infusion, oral and s.c.) in beagle dogs, provided with data from hematological examinations. We set the following criteria as a positive response in the present survey: increases of 50% or more in either or both WBC or fibrinogen compared to the predosing value, transiently from Day 1 to Day 3 of the study. Among 25 studies surveyed, about 1/2 of the studies exhibited increases of 50% or more in either or both fibrinogen or WBC counts compared to the predosing values showing dose-dependency transiently on Day 1 or Day 2. These changes were remarkable after intravenous application. Oral application produced similar effects, although the incidence and severity were low compared to the i.v. routes. Regarding blood chemical and hematological changes other than changes in fibrinogen and WBC counts, there were no essential differences between the groups of studies with and without the changes in fibrinogen and WBC counts. These changes were thought to be characteristic and to have occurred as incidents unrelated to other changes. The reported changes seen in single-dose toxicity studies may belong to the category of APR as the non-specific mechanism of living bodies as stated by Burns et al. (1996). PMID:11429972

  9. Lamotrigine kidney distribution in male rats following a single intraperitoneal dose.

    PubMed

    Castel-Branco, M M; Falcão, A C; Figueiredo, I V; Macedo, T R A; Caramona, M M

    2004-02-01

    As it has been previously shown that lamotrigine (LTG) accumulates in the kidney of male rats, the purpose of the present investigation was to characterize the kidney profiles of LTG and its kidney distribution pattern in male rats, in order to confirm if a preferential distribution exists and to analyse if it does or does not affect the LTG systemic pharmacokinetics. Adult male Wistar rats were intraperitoneally injected with 5, 10 and 20 mg/kg of LTG. The concentration-time profiles of LTG in plasma and whole kidney were determined over 120 h postdose. The distribution of LTG in the rat kidney was investigated in another group of rats by measuring LTG levels in the renal cortex and medulla. The LTG plasma concentration-time profiles revealed a linear relationship with dose. However, a slight increase in the LTG elimination half-life with dose was observed. In contrast, a nonlinear relationship was established between LTG kidney levels and the dose administered. Consequently, nonparallel patterns were observed between LTG plasma and kidney profiles. The LTG kidney distribution pattern revealed an accumulation of LTG in the renal cortex. The present study demonstrated that LTG distributes preferentially to the kidneys of the male rat in a dose-dependent manner and suggests that such distribution may slightly affect the systemic kinetics of the drug. PMID:14748754

  10. Dosimetry of single fraction high dose total body irradiation as measured by thermoluminescent dosimeters

    SciTech Connect

    Liu, J.C.; Bacza, E.T.; Findley, D.O.; Forell, B.W.

    1983-09-01

    Eighty-five patients with acute myelogenous or acute lymphoblastic leukemia were treated at the Cit of Hope National Medicine Center with chemotherapy, total body irradiation, and bone marrow transplant. The average mid-line dose to these patients was 1002 rad with a uniformity of 8%.

  11. Two-fraction high-dose-rate brachytherapy within a single day combined with external beam radiotherapy for prostate cancer: single institution experience and outcomes

    PubMed Central

    Liu, Junyang; Kaidu, Motoki; Sasamoto, Ryuta; Ayukawa, Fumio; Yamana, Nobuko; Sato, Hiraku; Tanaka, Kensuke; Kawaguchi, Gen; Ohta, Atsushi; Maruyama, Katsuya; Abe, Eisuke; Kasahara, Takashi; Nishiyama, Tsutomu; Tomita, Yoshihiko; Aoyama, Hidefumi

    2016-01-01

    We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- (n =5; 3.2%), intermediate- (n =36; 23.1%) and high-risk (n =115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary. PMID:26983988

  12. Pharmacokinetics of a Single Dose of Oral and Subcutaneous Meloxicam in Caribbean Flamingos ( Phoenicopterus ruber ruber).

    PubMed

    Lindemann, Dana M; Carpenter, James W; KuKanich, Butch

    2016-03-01

    To determine the pharmacokinetics of meloxicam in Caribbean flamingos ( Phoenicopterus ruber ruber), a pilot study was performed first, followed by a complete pharmacokinetic study. Four healthy birds were divided into 2 groups and administered 1 mg/kg of either oral (n = 2) or subcutaneous (n = 2) meloxicam. Plasma meloxicam concentrations were determined with liquid chromatography-mass spectrometry. Based on the pilot study results, 12 healthy birds were assigned into 2 groups and administered either 3 mg/kg PO (n = 6) or 1.5 mg/kg SC (n = 6) of meloxicam. Blood samples were collected at baseline and at 9 time intervals per group after administration of meloxicam in all flamingos. Plasma concentrations after administration of 3 mg/kg PO meloxicam reached a mean maximum plasma concentration of 1.449 μg/mL at 2.35 hours with a terminal half-life of 1.832 hours. After administration of 1.5 mg/kg SC meloxicam, maximum plasma concentration was 4.059 μg/mL at 0.91 hour with a terminal half-life of 1.104 hours. The plasma profile from the main oral study (3 mg/kg PO) differed markedly from the pilot study (1 mg/kg PO), suggesting a delayed absorption with the higher dose and lack of dose proportionality. The different doses for subcutaneous administration resulted in a proportional change in plasma concentrations. Further studies are needed to evaluate the effects of the drug volume administered and fasting status when oral dosing is used. Future studies are also needed to investigate multiple-dose pharmacokinetics of meloxicam and to determine the therapeutic meloxicam plasma concentration in Caribbean flamingos. PMID:27088740

  13. Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies

    PubMed Central

    Beamer, Edward; Sills, Graeme J.; Thippeswamy, Thimmasettappa

    2014-01-01

    A refined kainate (KA) C57BL/6J mouse model of status epilepticus (SE) using a repeated low dose (RLD) of KA (5 mg/kg, intraperitoneal; at 30 min intervals) was compared with the established single high dose (SHD) of KA (20 mg/kg, intraperitoneal) model. In the RLD group, increased duration of convulsive motor seizures (CMS, Racine scale stage ≥3) with a significant reduction in mortality from 21% to 6% and decreased variability in seizure severity between animals/batches were observed when compared to the SHD group. There was a significant increase in the percentage of animals that reached stage-5 seizures (65% versus 96%) in the RLD group. Integrated real-time video-EEG analysis of both groups, using NeuroScore software, revealed stage-specific spikes and power spectral density characteristics. When the seizures progressed from non-convulsive seizures (NCS, stage 1–2) to CMS (stage 3–5), the delta power decreased which was followed by an increase in gamma and beta power. A transient increase in alpha and sigma power marked the transition from NCS to CMS with characteristic ‘high frequency trigger’ spikes on the EEG, which had no behavioral expression. During SE the spike rate was higher in the RLD group than in the SHD group. Overall these results confirm that RLD of KA is a more robust and consistent mouse model of SE than the SHD of KA mouse model. PMID:24802808

  14. Effects of feeding on the plasma disposition kinetics of the anthelmintic albendazole in laying hens.

    PubMed

    Bistoletti, M; Alvarez, L; Lanusse, C; Moreno, L

    2014-01-01

    1. To optimise the use of albendazole (ABZ) as an anthelmintic in hens, the effects of fasting and type of diet on the plasma kinetics of ABZ and its metabolites were evaluated. 2. Twenty-four hens were distributed into 4 groups: In experiment I the Fed group were fed ad libitum, while the Fasted group was fasted over a 12-h period. In experiment II the Pelleted group was fed with pelleted commercial food, while the Grain group was fed with cereal grains. All the groups were treated with ABZ by oral route. Blood samples were taken and plasma analysed by HPLC. 3. ABZ and its metabolites albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) were recovered in plasma in all the groups. The 12-h fasting period did not modify the disposition kinetics of ABZ in hens. The type of feed affected ABZ kinetics. ABZSO concentration profile was higher and detected for longer in the Grain group compared to the Pelleted group. Statistical differences were not found for AUC0-∞ values, whereas the T1/2for and T1/2el were different between groups. 4. Factors affecting ABZ kinetic behaviour should be taken into account to optimise its use to ensure the sustainability of the limited available anthelmintic therapeutic tools in avian parasite control. PMID:25159169

  15. Methimazole increases the plasma concentrations of the albendazole metabolites of netobimin in sheep.

    PubMed

    Lanusse, C E; Prichard, R K

    1992-03-01

    The influence of methimazole (MTZ) on the pharmacokinetics of netobimin (NTB) and its metabolites was investigated in adult sheep. NTB zwitterion suspension was administered at 20 mg kg-1 by intraruminal injection either alone or with simultaneous administration of MTZ intramuscularly at 1.5 mg kg-1. Blood samples were taken serially over a 120-h period and plasma was analysed by HPLC for NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO), and albendazole sulphone (ABZSO2). NTB parent drug showed fast absorption, low area under the plasma concentration-time curve (AUC) and was rapidly removed from plasma after both treatments. The presence of MTZ did increase significantly the ABZ AUC (138 per cent) and mean residence time (MRT) (86 per cent). Concomitant treatment with MTZ resulted in a notably higher ABZSO plasma profile with significantly longer elimination half-life (t1/2 beta) (390 per cent) and MRT (252 per cent) and with significantly higher AUC (95 per cent). Also, MTZ induced significant increases in ABZSO2 t1/2 beta, AUC, and MRT. We have demonstrated a pharmacokinetic interaction between MTZ and NTB metabolites. MTZ may alter the liver biotransformation of ABZ metabolites which results in pronounced changes in the disposition kinetics of anthelmintically active metabolites. PMID:1550912

  16. Precocious gut maturation and immune cell expansion by single dose feeding the lectin phytohaemagglutinin to suckling rats.

    PubMed

    Prykhod'ko, Olena; Fed'kiv, Olexandr; Linderoth, Ann; Pierzynowski, Stefan G; Weström, Björn R

    2009-03-01

    The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 microg/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 microg/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 microg/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21-28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process. PMID:18644165

  17. SU-E-I-98: Dose Comparison for Pulmonary Embolism CT Studies: Single Energy Vs. Dual Energy

    SciTech Connect

    Mahmood, U; Erdi, Y

    2014-06-01

    Purpose: The purpose of this study was to assess and compare the size specific dose estimate (SSDE), dose length product (DLP) and noise relationship for pulmonary embolism studies evaluated by single source dual energy computed tomography (DECT) against conventional CT (CCT) studies in a busy cancer center and to determine the dose savings provided by DECT. Methods: An IRB-approved retrospective study was performed to determine the CTDIvol and DLP from a subset of patients scanned with both DECT and CCT over the past five years. We were able to identify 30 breast cancer patients (6 male, 24 female, age range 24 to 81) who had both DECT and CCT studies performed. DECT scans were performed with a GE HD 750 scanner (140/80 kVp, 480 mAs and 40 mm) and CCT scans were performed with a GE Lightspeed 16 slice scanner (120 kVp, 352 mAs, 20 mm). Image noise was measured by placing an ROI and recording the standard deviation of the mean HU along the descending aorta. Results: The average DECT patient size specific dose estimate was to be 14.2 ± 1.7 mGy as compared to 22.4 ± 2.7 mGy from CCT PE studies, which is a 37% reduction in the SSDE. The average DECT DLP was 721.8 ± 84.6 mGy-cm as compared to 981.8 ± 106.1 mGy-cm for CCT, which is a 26% decrease. Compared to CCT the image noise was found to decrease by 19% when using DECT for PE studies. Conclusion: DECT SSDE and DLP measurements indicate dose savings and image noise reduction when compared to CCT. In an environment that heavily debates CT patient doses, this study confirms the effectiveness of DECT in PE imaging.

  18. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria.

    PubMed

    Charman, Susan A; Arbe-Barnes, Sarah; Bathurst, Ian C; Brun, Reto; Campbell, Michael; Charman, William N; Chiu, Francis C K; Chollet, Jacques; Craft, J Carl; Creek, Darren J; Dong, Yuxiang; Matile, Hugues; Maurer, Melanie; Morizzi, Julia; Nguyen, Tien; Papastogiannidis, Petros; Scheurer, Christian; Shackleford, David M; Sriraghavan, Kamaraj; Stingelin, Lukas; Tang, Yuanqing; Urwyler, Heinrich; Wang, Xiaofang; White, Karen L; Wittlin, Sergio; Zhou, Lin; Vennerstrom, Jonathan L

    2011-03-15

    Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC(50) values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei-infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death. PMID:21300861

  19. Effects of Age, Sex, and Obesity on the Single-Dose Pharmacokinetics of Omarigliptin in Healthy Subjects.

    PubMed

    Addy, Carol; Tatosian, Daniel A; Glasgow, Xiaoli S; Iii, Isaias Noel Gendrano; Sisk, Christine McCrary; Kauh, Eunkyung A; Stoch, S Aubrey; Wagner, John A

    2016-09-01

    Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential. Plasma was collected at selected postdose times for evaluation of omarigliptin concentrations. Pharmacokinetic parameters were compared with historical data from a previously-conducted single-dose study in young, healthy, nonobese men. There were no clinically significant differences in omarigliptin AUC0-∞ , the primary pharmacokinetic parameter for assessing efficacy and safety, based on age, sex, or BMI (pooled nonobese elderly versus pooled nonobese young, young nonobese female versus young nonobese male, and pooled young obese versus pooled young nonobese). There were no serious adverse events or hypoglycemic events attributable to omarigliptin administration. Demographic factors and BMI had no meaningful effect on omarigliptin pharmacokinetics, suggesting that dose adjustment based on age, sex, or obesity is not required. PMID:27627193

  20. Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial.

    PubMed Central

    Geelhoed, G. C.; Turner, J.; Macdonald, W. B.

    1996-01-01

    OBJECTIVE--To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital. DESIGN--Double blind, randomised, placebo controlled clinical trial. SETTING--The emergency department of a tertiary paediatric hospital. SUBJECTS--100 children aged 4-122 months presenting with mild croup. INTERVENTION--A single oral dose of dexamethasone 0.15 mg/kg or placebo. MAIN OUTCOME MEASURE--Return to medical care with ongoing croup. RESULTS--Baseline characteristics of the two treatment groups were similar. Eight children (all from the placebo group) returned to medical care with ongoing croup, one being admitted. There was no reported difference in duration of croup symptoms, duration of viral symptoms, or rate of return to medical care for other reasons. CONCLUSION--Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup. PMID:8688774

  1. Cellular Inflammatory Infiltrate in Pneumonitis Induced by a Single Moderate Dose of Thoracic X Radiation in Rats

    PubMed Central

    Szabo, Sara; Ghosh, Swarajit N.; Fish, Brian L.; Bodiga, Sreedhar; Tomic, Rade; Kumar, Gagan; Morrow, Natalya V.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2010-01-01

    The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis. PMID:20334527

  2. Predicting Radiosensitivity with Gamma-H2AX Foci Assay after Single High-Dose-Rate and Pulsed Dose-Rate Ionizing Irradiation.

    PubMed

    van Oorschot, Bregje; Hovingh, Suzanne; Dekker, Annelot; Stalpers, Lukas J; Franken, Nicolaas A P

    2016-02-01

    Gamma-H2AX foci detection is the standard method to quantify DNA double-strand break (DSB) induction and repair. In this study, we investigated the induction and decay of γ-H2AX foci of different tumor cell lines and fibroblasts with known mutations in DNA damage repair genes, including ATM, LigIV, DNA-PKcs, Rad51 and Rad54. A radiation dose of 2.4 Gy was used for either an acute single high-dose-rate (sHDR) exposure or a pulsed dose-rate (pDR) exposure over 24 h. The number of γ-H2AX foci was determined at 30 min and 24 h after sHDR irradiation and directly after pDR irradiation. In a similar manner, γ-H2AX foci were also examined in lymphocytes of patients with differences in normal tissue toxicity after a total radiation dose of 1 Gy. In an initial count of the number of foci 30 min after sHDR irradiation, repair-proficient cell types could not be distinguished from repair-deficient cell types. However at 24 h postirradiation, while we observed a large decrease in foci numbers in NHEJ-proficient cells, the amount of γ-H2AX foci in cell types with mutated NHEJ repair remained at high levels. Except for IRS-1SF cells, HR-deficient cell types eventually did show a moderate decrease in foci number over time, albeit to a lesser extent than their corresponding parentals or repair-proficient control cells. In addition, analysis of γ-H2AX foci after sHDR exposure of patients with different sensitivity status clearly showed individual differences in radiation response. Radiosensitive patients could be distinguished from the more radioresistant patients with γ-H2AX foci decay ratios (initial number of foci divided by residual number of foci). Significantly higher decay ratios were observed in patients without toxicities, indicating more proficient repair compared to patients with radiation-induced side effects. After pDR irradiation, no consistent correlation could be found between foci number and radiosensitivity. In conclusion, γ-H2AX formation is a rapid and

  3. A single TLD dose algorithm to satisfy federal standards and typical field conditions

    SciTech Connect

    Stanford, N.; McCurdy, D.E. )

    1990-06-01

    Modern whole-body dosimeters are often required to accurately measure the absorbed dose in a wide range of radiation fields. While programs are commonly developed around the fields tested as part of the National Voluntary Accreditation Program (NVLAP), the actual fields of application may be significantly different. Dose algorithms designed to meet the NVLAP standard, which emphasizes photons and high-energy beta radiation, may not be capable of the beta-energy discrimination necessary for accurate assessment of absorbed dose in the work environment. To address this problem, some processors use one algorithm for NVLAP testing and one or more different algorithms for the work environments. After several years of experience with a multiple algorithm approach, the Dosimetry Services Group of Yankee Atomic Electric Company (YAEC) developed a one-algorithm system for use with a four-element TLD badge using Li2B4O7 and CaSO4 phosphors. The design of the dosimeter allows the measurement of the effective energies of both photon and beta components of the radiation field, resulting in excellent mixed-field capability. The algorithm was successfully tested in all of the NVLAP photon and beta fields, as well as several non-NVLAP fields representative of the work environment. The work environment fields, including low- and medium-energy beta radiation and mixed fields of low-energy photons and beta particles, are often more demanding than the NVLAP fields. This paper discusses the development of the algorithm as well as some results of the system testing including: mixed-field irradiations, angular response, and a unique test to demonstrate the stability of the algorithm. An analysis of the uncertainty of the reported doses under various irradiation conditions is also presented.

  4. The influence of frame alignment with dose compensation on the quality of single particle reconstructions.

    PubMed

    Spear, John M; Noble, Alex J; Xie, Qing; Sousa, Duncan R; Chapman, Michael S; Stagg, Scott M

    2015-11-01

    As direct electron detection devices in cryo-electron microscopy become ubiquitous, the field is now ripe for new developments in image analysis techniques that take advantage of their increased SNR coupled with their high-throughput frame collection abilities. In approaching atomic resolution of native-like biomolecules, the accurate extraction of structural locations and orientations of side-chains from frames depends not only on the electron dose that a sample receives but also on the ability to accurately estimate the CTF. Here we use a new 2.8Å resolution structure of a recombinant gene therapy virus, AAV-DJ with Arixtra, imaged on an FEI Titan Krios with a DE-20 direct electron detector to probe new metrics including relative side-chain density and ResLog analysis for optimizing the compensation of electron beam damage and to characterize the factors that are limiting the resolution of the reconstruction. The influence of dose compensation on the accuracy of CTF estimation and particle classifiability are also presented. We show that rigorous dose compensation allows for better particle classifiability and greater recovery of structural information from negatively charged, electron-sensitive side-chains, resulting in a more accurate macromolecular model. PMID:26391007

  5. Comparative Metabolism Studies of Hexabromocyclododecane (HBCD) Diastereomers in Male Rats Following a Single Oral Dose.

    PubMed

    Hakk, Heldur

    2016-01-01

    Male Sprague-Dawley rats were dosed orally with 3 mg/kg of one of three hexabromocyclododecane (HBCD) diastereomers. Each diastereomer was well absorbed (73-83%), and distributed preferentially to lipophilic tissues. Feces were the major route of excretion; cumulatively accounting for 42% of dose for α-HBCD, 59% for ß-HBCD, and 53% for γ-HBCD. Urine was also an important route of HBCD excretion, accounting for 13% of dose for α-HBCD, 30% for ß-HBCD, and 21% for γ-HBCD. Total metabolism of HBCD diastereomers followed the rank order ß > γ > α, and was >65% of that administered. The metabolites formed were distinct in male rats: α-HBCD did not debrominate or stereoisomerize, but formed two hydroxylated metabolites; ß- and γ-HBCD were both extensively metabolized via pathways of stereoisomerization, oxidation, dehydrogenation, reductive debromination, and ring opening. ß-HBCD was biotransformed to two mercapturic acid pathway metabolites. The metabolites of ß- and γ-HBCD were largely distinct, and could possibly be used as markers of exposure. These isomer-specific data suggest that α-HBCD would be the most dominant HBCD diastereomer in biological tissues because it was metabolized to the lowest degree and also accumulated from the stereoisomerization of the β- and γ- diastereomers. PMID:26629593

  6. Bioavailability of a new oral formulation of medroxyprogesterone acetate compared with the standard formulation: a single dose randomized study.

    PubMed

    Kjaer, M; Brunsgaard, N; Jakobsen, P; Edwards, D M; Strolin-Benedetti, M

    1993-08-01

    Twenty-six female patients with breast cancer participated in an open, randomized, cross-over study comparing single dose bioavailability of a recently developed oral medroxyprogesterone acetate (MPA) formulation (200 mg sachet where MPA is loaded in a polyvinylpyrrolidone cross-linked polymer, MPA/PVP) with the standard formulation (500 mg tablet). Blood tests were performed under standardized conditions for 120 h in all patients and MPA plasma concentrations determined by means of HPLC. Dose-normalized AUC(0-tz), AUC (0-infinity) and Cmax were all significantly higher for the MPA/PVP formulation than for the standard formulation. The relative bioavailability of the MPA/PVP formulation was on average three times superior to that of the standard formulation. This new MPA formulation might have important clinical implications for the treatment of hormone-sensitive cancer. PMID:8400345

  7. Effects of single-dose irradiation in tumor blood flow studied by 15O decay after proton activation in situ.

    PubMed

    Emami, B; Ten Haken, R K; Nussbaum, G H; Hughes, W L

    1981-10-01

    A noninvasive technique employing photon activation of tissue oxygen in situ and detection of subsequent 15O positron decay was used to study the effects of single-dose 60Co irradiation on capillary blood flow in transplanted rat rhabdomyosarcomas. Tumor blood flow was measured before irradiation with 16.5, 38.5, or 60.5 Gy and at several intervals afterward (0-72 hr.). Pre-irradiation values of volume-averaged blood flow in the tumor ranged from 7 to 44 ml/min./100 g. Several hours after irradiation, blood flow fell by up to 50% for 60.5 Gy and up to 35% for 16.5 Gy. However, 24 hours after irradiation, tumor blood flow had recovered completely in the 16.5-Gy group and substantially in the others. For smaller doses such as the fractions typically employed in radiotherapy, no changes in tumor blood flow were observed. PMID:7291527

  8. Human metabolism and excretion kinetics of aniline after a single oral dose.

    PubMed

    Modick, Hendrik; Weiss, Tobias; Dierkes, Georg; Koslitz, Stephan; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger Martin

    2016-06-01

    Aniline is an important source material in the chemical industry (e.g., rubber, pesticides, and pharmaceuticals). The general population is known to be ubiquitously exposed to aniline. Thus, assessment of aniline exposure is of both occupational and environmental relevance. Knowledge on human metabolism of aniline is scarce. We orally dosed four healthy male volunteers (two fast and two slow acetylators) with 5 mg isotope-labeled aniline, consecutively collected all urine samples over a period of 2 days, and investigated the renal excretion of aniline and its metabolites by LS-MS/MS and GC-MS. After enzymatic hydrolysis of glucuronide and sulfate conjugates, N-acetyl-4-aminophenol was the predominant urinary aniline metabolite representing 55.7-68.9 % of the oral dose, followed by the mercapturic acid conjugate of N-acetyl-4-aminophenol accounting for 2.5-6.1 %. Acetanilide and free aniline were found only in minor amounts accounting for 0.14-0.36 % of the dose. Overall, these four biomarkers excreted in urine over 48 h post-dose represented 62.4-72.1 % of the oral aniline dose. Elimination half-times were 3.4-4.3 h for N-acetyl-4-aminophenol, 4.1-5.5 h for the mercapturic acid conjugate, and 1.3-1.6 and 0.6-1.2 h for acetanilide and free aniline, respectively. Urinary maximum concentrations of N-acetyl-4-aminophenol were reached after about 4 h and maximum concentrations of the mercapturic acid conjugate after about 6 h, whereas concentrations of acetanilide and free aniline peaked after about 1 h. The present study is one of the first to provide reliable urinary excretion factors for aniline and its metabolites in humans after oral dosage, including data on the predominant urinary metabolite N-acetyl-4-aminophenol, also known as an analgesic under the name paracetamol/acetaminophen. PMID:26233686

  9. Single-dose paravertebral blockade versus epidural blockade for pain relief after open renal surgery: A prospective randomized study

    PubMed Central

    Moawad, Hazem Ebrahem; Mousa, Sherif Abdo; El-Hefnawy, Ahmed S.

    2013-01-01

    Background: Paravertebral block (PVB) has been an established technique for providing analgesia to the chest and abdomen. We conducted the current study to compare single-dose PVB versus single-dose epidural blockade (EP) for pain relief after renal surgery. Methods: Eighty patients scheduled for renal surgery were randomly assigned into two groups according to the analgesic technique, PVB group or EP group. General anesthesia was induced for all patients. Postoperative pain was assessed over 24 h using 10-cm visual analog scale (VAS). Postoperative total pethidine consumption was recorded. Any postoperative events, such as nausea, vomiting, shivering, or respiratory complications, were recorded. Hemodynamics and blood gasometry were also recorded. Results: EP group showed significant decrease of both heart rate and mean blood pressure at most of the operative periods when compared with PVB group. There was no difference in total rescue analgesic consumption. Postoperative VAS showed no significant difference between the studied groups. Postoperative events were comparable in both the groups. Conclusion: Single injection PVB resulted in similar analgesia but greater hemodynamic stability than epidural analgesia in patients undergoing renal surgery, therefore this technique may be recommended for patients with coexisting circulatory disease. PMID:23717235

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

    PubMed

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

    2015-12-01

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

  11. Xenografts of five human leiomyosarcomas: radiation response after 60cobalt- and d(14)+Be neutron single doses.

    PubMed

    Budach, V; Stuschke, M; Budach, W; Streffer, C; Sack, H

    1990-01-01

    Five permanently established xenograft lines of human soft tissue sarcomas were irradiated with single doses of 5.8 MeV d(14)+Be neutrons and of 60Co rays, respectively, at several dose levels to generate dose response relationships. The tumors were clamped ten minutes prior to and during irradiation to induce uniform hypoxia. All tumours were previously characterized by means of histomorphology, tumour doubling times (DT's), DNA-index and enzyme pattern of the lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (GPD). According to these criteria, three out of five leiomyosarcomas were identical referring to the biopsy of origin, whereas two had changed in successive passages. For the different tumour lines, specific growth delays ranged from 0 to 8.7 after 5.3 Gy neutrons and from 0 to 11.4 after 16 Gy60Co, respectively. In terms of radiosensitivity for different single doses and irradiation qualities, a highly significant overall correlation (rs = 0.82 +/- 0.06) was found for the ranking of the tumours with respect to the growth delay and specific growth delay endpoints. No correlation was found between tumour doubling times and the relative biological effectiveness (RBE). In general, calculated RBE-values decreased with increasing effect level. For the five tumour lines, RBE-values ranged from 1.6 to 12.7 and 2.0 to 4.4 at specific growth delays of 0.5 and 2.0, respectively, under acutely hypoxic conditions. These results indicate a potential advantage for neutrons in a subgroup of human soft tissue sarcomas compared with sparsely ionising irradiation. PMID:2105535

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

    PubMed Central

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

    2013-01-01

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

  13. Safety trial of single-dose treatments with a combination of ivermectin and diethylcarbamazine in bancroftian filariasis.

    PubMed

    Moulia-Pelat, J P; Nguyen, L N; Glaziou, P; Chanteau, S; Gay, V M; Martin, P M; Cartel, J L

    1993-06-01

    A supervised safety trial of the treatment with a combination of ivermectin 400 micrograms.kg-1 (IVER 400) plus increasing doses of diethylcarbamazine (DEC), given simultaneously in single dose, was performed on five groups of Polynesian Wuchereria bancrofti carriers, 49 males aged 25 to 73 years, in whom microfilaremia ranged from 1 to 6,137 mf/ml. The trial was hospital-based, open, dose-escalating (1 group per week). Safety of an unchanging dose of IVER 400 and ascending doses of DEC were studied in the 5 following groups: group 1- IVER 400 plus DEC 1 mg.kg-1, 12 patients; group 2- IVER 400 plus DEC 3 mg.kg-1, 17 patients; group 3- IVER 400 plus DEC 6 mg.kg-1, 10 patients. Two control groups were included in the study, group 4- DEC 6 mg.kg-1 alone, 5 patients; group 5-: IVER 400 alone, 5 patients. Carriers were examined and questioned regarding their experience of adverse reactions, which were graded 0 to 3 according to severity, at 6, 12 and 24 hours and at 4 days after treatment. Biological examination was performed 4 days before and 4 days after treatment and included determination of microfilaremia, complete blood count, liver function tests and assessment of creatinine and urea levels. Adverse reactions were observed in 51% of 49 carriers (15 of grade 1, 8 of grade 2, 2 of grade 3). None was considered serious and they all disappeared in 2 days. The main symptoms were fever > or = 37.5 degrees C, myalgia, arthralgia, headache, asthenia, anorexia, vertigo and chills. Adverse reactions of patients were not significantly different between the five groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8367670

  14. Rizatriptan, a novel 5-HT1B/1D agonist for migraine: single- and multiple-dose tolerability and pharmacokinetics in healthy subjects.

    PubMed

    Goldberg, M R; Lee, Y; Vyas, K P; Slaughter, D E; Panebianco, D; Ermlich, S J; Shadle, C R; Brucker, M J; McLoughlin, D A; Olah, T V

    2000-01-01

    Rizatriptan is a novel 5-HT1D/1B agonist for relief of migraine headache. The pharmacokinetics, metabolite profiles, and tolerability of rizatriptan were examined in a multiple-dose study in healthy subjects. Rizatriptan (N = 24) (or placebo, N = 12) was administered as a single 10 mg dose, followed 48 hours later by administration of one 10 mg dose every 2 hours for three doses on 4 consecutive days, corresponding to the maximum daily dose for a migraine attack. The AUC of rizatriptan and its active N-monodesmethyl metabolite after three 10 mg doses was approximately threefold greater than the plasma concentrations following a single 10 mg dose. Metabolite profiles were similar after single and multiple doses. Adverse events during rizatriptan were mild and transient; similar events occurred during placebo, with a somewhat reduced incidence. Diastolic blood pressure tended to increase compared with placebo (approximately 5 mmHg), particularly on the first multiple-dose day (p < .01 vs. placebo). In conclusion, rizatriptan is well tolerated by healthy subjects during multiple-dose administration, with no unexpected accumulation of drug in plasma. PMID:10631625

  15. Thiol dosing of ZnO single crystals and nanorods: Surface chemistry and photoluminescence

    NASA Astrophysics Data System (ADS)

    Singh, Jagdeep; Im, Jisun; Watters, Evan J.; Whitten, James E.; Soares, Jason W.; Steeves, Diane M.

    2013-03-01

    Adsorption of thiols on ZnO(0001) and ZnO nanorods has been investigated using X-ray and ultraviolet photoelectron spectroscopies (XPS and UPS). Ultrahigh vacuum (UHV) dosing of sputter-cleaned ZnO(0001) with methanethiol (MT), 1-dodecanethiol (DDT), and 3-mercaptopropyltrimethoxysilane (MPTMS) leads to S2p peaks with a binding energy of 163.3 eV. Similar results for MPTMS are obtained for sputter-cleaned ZnO(0001) that is pre-dosed with water to form hydroxyl groups. In all cases, the absence of a free thiol S2p peak at 164.2 eV indicates that bonding to the surface occurs via the thiol end of the molecule. A DDT-dosed ZnO(0001) sample stored for 10 days in UHV and heated to temperatures as high as 150 °C exhibits minimal changes in its S/Zn atomic ratio, confirming chemisorption and the presence of a strong bond to the surface. UPS shows that MT adsorption on sputtered ZnO(0001) leads to a 0.7 eV increase in work function and perturbation of the MT molecular orbitals, again consistent with chemisorption. Dry ZnO nanorods have been exposed to MT while monitoring their photoluminescence. XPS and Raman spectroscopy confirm thiol adsorption. Relative to dry ZnO, adsorption causes a decrease in intensity of the visible emission peak, but the UV peak remains unchanged. These results indicate that Znsbnd S bond formation quenches radiative decay to the valence band from defect states, possibly by methanethiolate adsorption filling oxygen vacancies.

  16. Can low-dose combination products for inhalation be formulated in single crystalline particles?

    PubMed

    Kumon, Michiko; Kwok, Philip Chi Lip; Adi, Handoko; Heng, Desmond; Chan, Hak-Kim

    2010-04-16

    This study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and mannitol as a crystalline excipient. Two formulations comprising widely used ICS and LABA were studied: budesonide/formoterol fumarate dihydrate/mannitol (B/F/M-SD) and fluticasone propionate/salmeterol xinafoate/mannitol (F/S/M-SD). Various physicochemical properties of the powders were analyzed. Aerosol performance was evaluated by dispersing each powder from an Aerolizer at 60 and 100 L/min into a Next Generation Impactor. We obtained partially hollow spherical particles (volume median diameters of 2 microm) with drug-enriched surfaces. Both formulations contained alpha-mannitol, and the ICSs were crystalline. The content of each drug component in the powder was found to conform to the theoretical dose. The ternary powders generated high fine particle fractions (>50% of the loaded dose), with concomitant drug deposition on the impactor stages. The aerosol performance of B/F/M-SD was maintained after storage over silica gel at 22 degrees C for 11 weeks. In conclusion, co-spray dried particles of ICS/LABA/M-SD were largely crystalline, stable and showed excellent aerosol performance. They may provide an attractive alternative strategy to develop combination products without lactose blends. PMID:20172026

  17. A single fixed-dose combination for all patients is bad medicine.

    PubMed

    Spence, J David

    2014-05-01

    It has been proposed that cardiovascular risk could be markedly reduced by prescribing a single daily pill to all patients at risk. This concept is bad medicine, because each constituent has problems, and the problems are different for each patient. A key principle of clinical pharmacology is individualization of therapy. Patients are not all the same, so a single polypill cannot work for all of them. For patients with resistant hypertension, at least 3 different versions would be needed for patients with different causes of hypertension, and even then not one pill would be suitable for all patients. PMID:24684856

  18. Comparison of single-dose oral grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in men. The STD Study Group.

    PubMed Central

    Hook, E W; McCormack, W M; Martin, D; Jones, R B; Bean, K; Maroli, A N

    1997-01-01

    In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males. PMID:9257777

  19. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose

    PubMed Central

    Tsuda, Yoshimi; Parkins, Christopher J.; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A.

    2015-01-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a ‘disseminating’ vaccine to target these viruses in wild African great apes. PMID:25820063

  20. Calcium absorption in corticoid treated subjects effects of a single oral dose of calcitriol.

    PubMed

    Colette, C; Monnier, L; Pares Herbute, N; Blotman, F; Mirouze, J

    1987-07-01

    We compared the fractional absorption of calcium (FACa, 6 h, % TD) and the radiocalcium transit (% TD per min) in seven glucocorticoid-treated patients (10-25 mg prednisolone per day) and in seven normal subjects, in the basal state and 12 h after an oral dose of synthetic 1,25-(OH)2D (3 micrograms). In the basal state, the radiocalcium transit was significantly decreased (P less than 0.02) at 15 min in patients treated with prednisolone, but FACa at 6 h was not significantly decreased (51 +/- 5 vs. 60 +/- 5% TD). 12 h after an oral dose of 1,25-(OH)2D which resulted in supraphysiologic plasma levels, FACa increased significantly (P less than 0.02) in both groups but the peak absorption rate of Ca remained lower in the corticoid-treated patients than in controls (P less than 0.02). The results suggest that glucocorticoids decrease the 1,25-(OH)2D-dependent transport of calcium across the proximal small intestine. PMID:3623424

  1. Response of mouse epidermal cells to single doses of heavy-particles

    NASA Technical Reports Server (NTRS)

    Leith, J. T.; Schilling, W. A.; Welch, G. P.

    1972-01-01

    The survival of mouse epidermal cells to heavy-particles has been studied In Vivo by the Withers clone technique. Experiments with accelerated helium, lithium and carbon ions were performed. The survival curve for the helium ion irradiations used a modified Bragg curve method with a maximum tissue penetration of 465 microns, and indicated that the dose needed to reduce the original cell number to 1 surviving cell/square centimeters was 1525 rads with a D sub o of 95 rads. The LET at the basal cell layer was 28.6 keV per micron. Preliminary experiments with lithium and carbon used treatment doses of 1250 rads with LET's at the surface of the skin of 56 and 193 keV per micron respectively. Penetration depths in skin were 350 and 530 microns for the carbon and lithium ions whose Bragg curves were unmodified. Results indicate a maximum RBE for skin of about 2 using the skin cloning technique. An attempt has been made to relate the epidermal cell survival curve to mortality of the whole animal for helium ions.

  2. Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

    PubMed Central

    Liem-Moolenaar, Marieke; Rad, Mandana; Zamuner, Stefano; Cohen, Adam F; Lemme, Francesca; Franson, Kari L; van Gerven, Joop M A; Pich, Emilio Merlo

    2011-01-01

    AIM Several lines of evidence suggest a possible role of 5-HT6receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established. PMID:21223356

  3. Pharmacokinetics of aclidinium bromide/formoterol fumarate fixed-dose combination compared with individual components: A phase 1, open-label, single-dose study.

    PubMed

    Fuhr, Rainard; Leselbaum, Anne; Aubets, Jordi

    2016-03-01

    Inhaled, long-acting bronchodilators represent a cornerstone of maintenance treatment for chronic obstructive pulmonary disease (COPD). Aclidinium bromide/formoterol fumarate 400/12 μg fixed-dose combination (FDC) has recently been licensed for use in adults with COPD in the European Union. This phase 1, randomized, open-label, 3-way, complete crossover, single-dose study assessed the pharmacokinetics, safety, and tolerability of an FDC, aclidinium bromide 400 μg, and formoterol fumarate 12 μg, all administered via Genuair™ to 30 healthy subjects. The rate and extent of absorption were comparable for aclidinium/formoterol FDC and individual monotherapies; aclidinium/formoterol FDC and aclidinium alone: Cmax , 270 and 215 pg/mL, respectively; AUC0-t , 229 and 222 pg · h/mL, respectively; aclidinium/formoterol FDC and formoterol alone: Cmax , 11 and 9.3 pg/mL, respectively; AUC, 36 and 32.4 pg · h/mL, respectively. There were no major differences in relative bioavailability between the combination and monotherapies: the aclidinium Cmax and AUC0-t were 26% and 3% higher, respectively, with aclidinium/formoterol FDC compared with aclidinium alone, and 18% and 11% higher, respectively, compared with formoterol alone. Aclidinium/formoterol FDC was well tolerated; the incidence of adverse events was low and similar to the monotherapies. Aclidinium/formoterol FDC was not associated with any major differences in rate and extent of absorption or relative bioavailability compared with monotherapies. PMID:27138024

  4. Prophylaxis in gynaecological and obstetric surgery: a comparative randomised multicentre study of single-dose cefotetan versus two doses of cefazolin.

    PubMed

    Periti, P; Mazzei, T; Periti, E

    1988-08-01

    Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3052893

  5. Comparison of single-dose ibuprofen lysine, acetylsalicylic acid, and placebo for moderate-to-severe postoperative dental pain.

    PubMed

    Nelson, S L; Brahim, J S; Korn, S H; Greene, S S; Suchower, L J

    1994-01-01

    In a single-dose, double-blind, parallel-group, single-site study, ibuprofen lysine 200 mg (IBL 200) was compared with acetylsalicylic acid 500 mg (ASA 500) and placebo in 183 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, duration and degree of analgesia, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, global evaluation, and requirement for additional analgesic medication; both IBL 200 and ASA 500 were significantly more effective than placebo. IBL 200 also had a significantly faster onset of action, greater peak and overall analgesic effect, and longer duration of analgesia than ASA 500. All treatments were generally well tolerated. PMID:7923312

  6. Chlamydial cervicitis and urethritis: single dose treatment compared with doxycycline for seven days in community based practises.

    PubMed Central

    Thorpe, E M; Stamm, W E; Hook, E W; Gall, S A; Jones, R B; Henry, K; Whitworth, G; Johnson, R B

    1996-01-01

    STUDY GOAL: To compare the efficacy and safety of single 1 g oral azithromycin with doxycycline, 100 mg twice daily for seven days for treatment of uncomplicated urogenital chlamydial infection. STUDY DESIGN: Randomised, unblinded, comparative trial, involving 597 patients demonstrating clinical evidence of genital chlamydia and a positive non-culture assay for Chlamydia trachomatis. RESULTS: Among the azithromycin- and doxycycline-treated patients 61% and 60%, respectively, were asymptomatic within one week after the first dose. At two weeks, these figures increased to 86% and 83%, respectively. Bacteriological eradication, based on a negative assay, occurred in 338 (97%) of 347 azithromycin-treated patients and 161 (99%) of 163 doxycycline-treated patients. CONCLUSION: Treatment of uncomplicated chlamydial cervicitis and urethritis with single 1 g oral azithromycin is equivalent to standard therapy with doxycycline. Drug-related adverse events were approximately twice as common as previously reported for both drugs. PMID:8698374

  7. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    PubMed

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653). PMID:26691247

  8. Safety and Immunogenicity of a Single Low Dose or High Dose of Clade 2 Influenza A(H5N1) Inactivated Vaccine in Adults Previously Primed With Clade 1 Influenza A(H5N1) Vaccine.

    PubMed

    Winokur, Patricia L; Patel, Shital M; Brady, Rebecca; Chen, Wilbur H; El-Kamary, Samer S; Edwards, Kathryn; Creech, C Buddy; Frey, Sharon; Keitel, Wendy A; Belshe, Robert; Walter, Emmanuel; Bellamy, Abbie; Hill, Heather

    2015-08-15

    Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-μg or 90-μg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine. PMID:25712967

  9. Comparative hazard identification by a single dose lung exposure of zinc oxide and silver nanomaterials in mice.

    PubMed

    Gosens, Ilse; Kermanizadeh, Ali; Jacobsen, Nicklas Raun; Lenz, Anke-Gabriele; Bokkers, Bas; de Jong, Wim H; Krystek, Petra; Tran, Lang; Stone, Vicki; Wallin, Håkan; Stoeger, Tobias; Cassee, Flemming R

    2015-01-01

    Comparative hazard identification of nanomaterials (NMs) can aid in the prioritisation for further toxicity testing. Here, we assessed the acute lung, systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage fluid (BALF) after administration of both non-functionalised and functionalised ZnO. The latter also induced systemic inflammation measured as an increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic inflammation. A decrease in glutathione levels was demonstrated in the liver following exposure to high doses of all three nanomaterials irrespective of any noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark dose (BMD) modeling statistics to compare potencies of the NMs, we rank functionalised ZnO ranked the highest based on the largest number of affected endpoints, as well as the strongest responses observed after 24 hours. The non-functionalised ZnO NM gave an almost similar response, whereas Ag NM did not cause an acute response at similar doses. PMID:25966284

  10. Comparative Hazard Identification by a Single Dose Lung Exposure of Zinc Oxide and Silver Nanomaterials in Mice

    PubMed Central

    Gosens, Ilse; Kermanizadeh, Ali; Jacobsen, Nicklas Raun; Lenz, Anke-Gabriele; Bokkers, Bas; de Jong, Wim H.; Krystek, Petra; Tran, Lang; Stone, Vicki; Wallin, Håkan; Stoeger, Tobias; Cassee, Flemming R.

    2015-01-01

    Comparative hazard identification of nanomaterials (NMs) can aid in the prioritisation for further toxicity testing. Here, we assessed the acute lung, systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage fluid (BALF) after administration of both non-functionalised and functionalised ZnO. The latter also induced systemic inflammation measured as an increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic inflammation. A decrease in glutathione levels was demonstrated in the liver following exposure to high doses of all three nanomaterials irrespective of any noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark dose (BMD) modeling statistics to compare potencies of the NMs, we rank functionalised ZnO ranked the highest based on the largest number of affected endpoints, as well as the strongest responses observed after 24 hours. The non-functionalised ZnO NM gave an almost similar response, whereas Ag NM did not cause an acute response at similar doses. PMID:25966284

  11. Effects of single-dose morning and evening administration of pravastatin on antioxidant markers in cholesterol-fed rabbits

    PubMed Central

    Kamal, Sahar Mohamed

    2011-01-01

    Background Accurate timing of statin administration is considered important to obtain the best hypolipidemic effect. Pravastatin is one of the currently prescribed hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, and was chosen in this study to evaluate its antioxidant effect when administered as a single daily dose in the morning versus evening in cholesterol-fed rabbits. Methods This 12-week study was performed in New Zealand rabbits, divided into four groups (n = 6 each), ie, normocholesterolemic controls; cholesterol 1% diet, nontreated ; cholesterol 1% diet treated with pravastatin in the morning; and cholesterol 1% diet treated with pravastatin in the evening. Plasma total cholesterol levels, superoxide dismutase enzyme levels in erythrocyte lysates, thiobarbituric acid-reactive substance content, catalase, and glutathione enzyme activity in liver homogenates from the tested rabbits were measured. Results Both morning and evening treatment with pravastatin significantly improved all the measured antioxidant markers in comparison with nontreated cholesterol-fed rabbits. However, results obtained with evening dosing were better than with morning dosing. Conclusion The antioxidant profile of pravastatin is better when the drug is administered in the evening rather than in the morning.

  12. Effects of Four Different Meal Types on the Population Pharmacokinetics of Single-Dose Rifapentine in Healthy Male Volunteers▿

    PubMed Central

    Zvada, Simbarashe P.; Van Der Walt, Jan-Stefan; Smith, Peter J.; Fourie, P. Bernard; Roscigno, Giorgio; Mitchison, Denis; Simonsson, Ulrika S. H.; McIlleron, Helen M.

    2010-01-01

    Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches. PMID:20516273

  13. Single-dose pharmacokinetics of oxytetracycline and penicillin G in tammar wallabies (Macropus eugenii).

    PubMed

    McLelland, D J; Barker, I K; Crawshaw, G; Hinds, L A; Spilsbury, L; Johnson, R

    2011-04-01

    The pharmacokinetics of oxytetracycline and penicillin G was investigated in tammar wallabies (Macropus eugenii). Groups of eight healthy tammar wallabies were administered i.v. oxytetracycline hydrochloride (40 mg/kg), i.m. long-acting-oxytetracycline (20 mg/kg), i.v. sodium penicillin G (30 mg/kg), or i.m. procaine/benzathine penicillin G (30 mg/kg). Plasma concentrations of oxytetracycline were determined using high-performance liquid chromatography. Pharmacokinetic parameters were comparable to those reported for eutherians of equivalent size and suggest that the practice of adjusting allometrically scaled doses to account for the lower metabolic rate of marsupials may not be valid. Long-acting oxytetracycline and penicillin G both demonstrated depot effects. However, the plasma concentrations achieved question the therapeutic efficacy of the long-acting preparations. PMID:21395607

  14. Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.

    PubMed

    Lee, Hee Joo; Joung, Sun Koung; Kim, Yoon Gyoon; Yoo, Jeong-Yeon; Han, Sang Beom

    2004-01-01

    A bioequivalence study of the ambroxol hydrochloride tablets was conducted. Twenty-four healthy male Korean volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week washout period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography (HPLC) for over a period of 24h after the administration. AUC(t) (the area under the plasma concentration-time curve from time 0 to last sampling time, 24h) was calculated by the linear-log trapezoidal rule method. C(max) (maximum plasma drug concentration) and T(max) (time to reach C(max)) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was 495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the reference medication, respectively. The point estimates and 90% confidence intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These results indicate that the two medications of ambroxol hydrochloride are bioequivalent and, thus, may be prescribed interchangeably. PMID:14597158

  15. Embryotoxicity of a single dose of medroxyprogesterone acetate (MPA) and maternal serum MPA concentrations in cynomolgus monkey (Macaca fascicularis).

    PubMed

    Prahalada, S; Carroad, E; Cukierski, M; Hendrickx, A G

    1985-12-01

    A single dose of MPA (Depo-Provera; Upjohn Co., Kalamazoo, Michigan) was administered intramuscularly to 12 time-mated pregnant cynomolgus monkeys on day 27 (+/- 2) of gestation at 25 mg/kg or at 100 mg/kg. Maternal blood samples were collected immediately prior to MPA injection and then at regular intervals until cesarean section at term (day 152 +/- 3). Infants in both dose groups had external genital abnormalities. Female infants in the low-dose groups had partial or complete labial fusion, prominent median raphe, and clitoral hypertrophy; at high doses (100 mg/kg), the female infants had complete labial fusion and a distinct penile urethra. MPA had an opposite effect on external genitalia of male infants. The penis was short and the scrotal swelling was absent or less conspicuous, and two males had hypospadias. The adrenal glands were significantly smaller (P less than 0.05) in infants of both sexes treated with 100 mg/kg. One of the infants treated with 25 mg/kg of MPA had a muscular ventricular septal defect. Serum concentrations of MPA were determined by radioimmunoassay in eight pregnant monkeys. In the 25 mg/kg group the patterns of MPA profiles in the serum were similar in all four animals. An initial peak occurred at 24-48 hr postinjection (2.7-9.6 ng/ml), followed by a slight decrease at 3 days postinjection (gestational day 30), and then a steady increase to maximum levels of 10-14 ng/ml occurring between gestational days 37 and 50. Serum levels gradually declined to concentrations below 5 ng/ml by midgestation in three of four monkeys. By comparison, both the patterns and magnitude of MPA concentration showed great interanimal variation in the 100 mg/kg group. MPA was present in cord blood at measurable concentrations in infants at both dose groups; the levels ranged from 0.6 to 8.3 ng/ml, corresponding to 40-72% of the maternal concentrations. These results demonstrate that a single injection of MPA during early pregnancy causes selective

  16. The influence of age on the pharmacokinetics and pharmacodynamics of bemetizide and triamterene: a single and multiple dose study.

    PubMed

    Mühlberg, W; Mutschler, E; Hofner, A; Spahn-Langguth, H; Arnold, O

    2001-06-01

    Diuretics are a frequent cause of adverse drug effects in the elderly, many times involving drug-drug interactions. In addition, multiple chronic diseases, age-dependent pharmacokinetic and pharmacodynamic changes, and a decreased homeostatic capacity often complicate diuretic therapy in the elderly. The pharmacokinetics (area under the plasma concentration-time curve: AUC; peak concentration in plasma: c(max); time to reach peak concentration: t(max); terminal half-life: t(1/2)) and pharmacodynamics (urine flow rates and renal excretion rates of Na(+) at 1, 3, and 6 h after oral administration) of a fixed combination of 25 mg bemetizide and 50 mg triamterene were investigated in 15 elderly patients (age 70-84 years) and 10 young volunteers (age 18-30 years) after a single dose (day 1) and after multiple doses (at steady state, day 8). Compared with the young volunteers, mean plasma concentrations of bemetizide, triamterene, and the active triamterene metabolite were significantly higher in the elderly volunteers. These elevated plasma levels occurred after single dose and were even more pronounced after multiple dose in the elderly. While plasma concentrations and AUC of bemetizide, triamterene, and the active metabolite of triamterene were increasing in correlation to age of subjects and duration of therapy, urine flow and renal Na(+) excretion rates were decreasing at the same degree. At steady state conditions, practically no effect on urine flow and Na(+) excretion rates could be observed in the elderly patients (in contrast to the young volunteers) for the first 8 h after administration of bemetizide and triamterene. The lower the measured (endogenous) creatinine clearance was in all subjects, the higher were the plasma concentrations of bemetizide and triamterene, and the lower was the effect on pharmacodynamics (i.e. urine flow and renal Na(+) excretion rates). The glomerular filtration rate, known to be lower in the elderly (a priori), was apparently

  17. Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

    PubMed Central

    2009-01-01

    Background The population pharmacokinetics of artesunate (AS) and its active metabolite dihydroartemisinin (DHA) were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR) or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability) parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka) of 3.85 h-1. The population estimates of apparent clearance (CL/F) and volume of distribution (V2/F) for AS were 1190 L/h with 36.2% inter-individual variability (IIV) and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F) and central volume of distribution (V3/F) were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F)