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成年绵羊经口服和静脉给药后溴化物的药代动力学

Pharmacokinetics of bromide in adult sheep following oral and intravenous administration.

作者信息

Quast T A, Combs M D, Edwards S H

机构信息

School of Animal and Veterinary Science, Charles Sturt University, Wagga Wagga, New South Wales, Australia.

出版信息

Aust Vet J. 2015 Jan-Feb;93(1-2):20-5. doi: 10.1111/avj.12285.

Abstract

OBJECTIVE

To determine the pharmacokinetics of bromide in sheep after single intravenous (IV) and oral (PO) doses.

PROCEDURE

Sixteen Merino sheep were randomly assigned to two treatment groups and given 120 mg/kg bromide, as sodium bromide IV or potassium bromide PO. Serum bromide concentrations were determined by colorimetric spectrophotometry.

RESULTS

After IV administration the maximum concentration (Cmax ) was 822.11 ± 93.61 mg/L, volume of distribution (Vd ) was 0.286 ± 0.031 L/kg and the clearance (Cl) was 0.836 ± 0.255 mL/h/kg. After PO administration the Cmax was 453.86 ± 43.37 mg/L and the time of maximum concentration (Tmax ) was 108 ± 125 h. The terminal half-life (t½ ) of bromide after IV and PO administration was 387.93 ± 115.35 h and 346.72 ± 94.05 h, respectively. The oral bioavailability (F) of bromide was 92%. No adverse reactions were noted in either treatment group during this study. The concentration versus time profiles exhibited secondary peaks, suggestive of gastrointestinal cyclic redistribution of the drug.

CONCLUSIONS AND CLINICAL RELEVANCE

When administered PO, bromide in sheep has a long half-life (t½ ) of approximately 14 days, with good bioavailability. Potassium bromide is a readily available, affordable salt with a long history of medical use as an anxiolytic, sedative and antiseizure therapy in other species. There are a number of husbandry activities and flock level neurological conditions, including perennial ryegrass toxicosis, in which bromide may have therapeutic or prophylactic application.

摘要

目的

测定绵羊单次静脉注射(IV)和口服(PO)溴化物后的药代动力学。

程序

将16只美利奴绵羊随机分为两个治疗组,分别静脉注射120mg/kg溴化钠或口服120mg/kg溴化钾。采用比色分光光度法测定血清溴化物浓度。

结果

静脉注射后,最大浓度(Cmax)为822.11±93.61mg/L,分布容积(Vd)为0.286±0.031L/kg,清除率(Cl)为0.836±0.255mL/h/kg。口服后,Cmax为453.86±43.37mg/L,达峰时间(Tmax)为108±125小时。静脉注射和口服后溴化物的终末半衰期(t½)分别为387.93±115.35小时和346.72±94.05小时。溴化物的口服生物利用度(F)为92%。本研究期间,两个治疗组均未观察到不良反应。浓度-时间曲线呈现二次峰,提示药物在胃肠道的循环再分布。

结论及临床意义

绵羊口服溴化物后半衰期长(t½约为14天),生物利用度良好。溴化钾是一种易于获得、价格低廉的盐类,在其他物种中作为抗焦虑、镇静和抗惊厥药物已有悠久的医学应用历史。在许多饲养管理活动和群体水平的神经疾病中,包括多年生黑麦草中毒,溴化物可能具有治疗或预防作用。

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