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氯霉素在非泌乳牛体内的药代动力学

Pharmacokinetics of chloramphenicol in non-lactating cattle.

作者信息

Anderson K L, Neff-Davis C A, Davis L E, Koritz G D, Nelson D R

出版信息

J Vet Pharmacol Ther. 1983 Dec;6(4):305-13. doi: 10.1111/j.1365-2885.1983.tb00005.x.

Abstract

The pharmacokinetics and bioavailability of a formulation of chloramphenicol base in propylene glycol were determined following administration of single intravenous (i.v.) and subcutaneous (s.c.) 50 mg/kg doses of chloramphenicol to six non-lactating Holstein cows. Mean serum concentrations of chloramphenicol following i.v. administration of 50 mg/kg declined rapidly from a peak of greater than 100 micrograms/ml to 6.9 micrograms/ml at 12 h after administration. Serum concentrations were not detectable at 24 h after administration. The curve of serum concentrations vs time was characteristic of a two-compartment open model. Mean i.v. data gave a biological half-life of 4.3 h and a volume of distribution of the central compartment of 0.44 l/kg. Serum concentrations of chloramphenicol following s.c. administration of 50 mg/kg rose slowly to a broad peak near 20 micrograms/ml from 3 to 8 h after administration and then declined. These data were also analysed according to a two-compartment open model. The biological half-life was 4.2 h and the volume of distribution of the central compartment was 0.50 l/kg. Significant adverse reactions, including acute collapse, intravascular haemolysis and haemoglobinuria, were observed in cows when dosed i.v. Cows dosed s.c. exhibited local reactions at injection sites. The disadvantages of administration of 50 mg/kg doses of chloramphenicol base in propylene glycol appear to be significant and may outweight the potential advantages of parenteral use of the drug as presently formulated.

摘要

给六头非泌乳荷斯坦奶牛静脉注射(i.v.)和皮下注射(s.c.)50mg/kg剂量的氯霉素丙二醇制剂后,测定了氯霉素碱制剂的药代动力学和生物利用度。静脉注射50mg/kg剂量的氯霉素后,氯霉素的平均血清浓度从给药后12小时大于100μg/ml的峰值迅速下降至6.9μg/ml。给药后24小时血清浓度检测不到。血清浓度与时间的曲线符合二室开放模型的特征。静脉注射的平均数据显示生物半衰期为4.3小时,中央室的分布容积为0.44l/kg。皮下注射50mg/kg剂量的氯霉素后,血清浓度在给药后3至8小时缓慢上升至接近20μg/ml的宽峰,然后下降。这些数据也根据二室开放模型进行了分析。生物半衰期为4.2小时,中央室的分布容积为0.50l/kg。静脉给药的奶牛出现了严重的不良反应,包括急性虚脱、血管内溶血和血红蛋白尿。皮下给药的奶牛在注射部位出现局部反应。在丙二醇中注射50mg/kg剂量的氯霉素碱的缺点似乎很明显,可能超过了目前制剂中该药物肠胃外使用的潜在优势。

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