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甲氧苄啶在虹鳟(Oncorhynchus mykiss)体内的处置动力学。

Disposition kinetics of trimethoprim in rainbow trout (Oncorhynchus mykiss).

作者信息

Tan W P, Wall R A

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

出版信息

Xenobiotica. 1995 Mar;25(3):315-29. doi: 10.3109/00498259509061855.

Abstract
  1. The pharmacokinetics of trimethoprim (TMP) following intra-aortic administration were investigated in rainbow trout. 2. The disposition kinetics for TMP were best described by a three-compartment open model. The disappearance of TMP from fish blood was characterized by rapid and pronounced distribution phases and a slow terminal elimination phase. 3. In contrast with pharmacokinetic data of TMP in mammals, the present study documented a long terminal elimination t1/2(36.1 h), large Vdss(5980 ml/kg) and small Clb(2.4 ml/min/kg) for TMP in rainbow trout, thus illustrating the slow biotransformation and elimination capacity, particularly the strong 'holding' capacity (storage) for the drug in trout. 4. The pharmacokinetic profiles in the present study indicated no dose dependency of TMP following three different bolus doses (5, 10 and 50 mg/kg). Hence, the first-order kinetic assumption was verified. 5. Urinary excretion of TMP was a minor elimination route in trout (14.4% dose).
摘要
  1. 在虹鳟鱼中研究了主动脉内给药后甲氧苄啶(TMP)的药代动力学。2. TMP的处置动力学最好用三室开放模型来描述。TMP从鱼血中的消失表现为快速且明显的分布阶段和缓慢的终末消除阶段。3. 与TMP在哺乳动物中的药代动力学数据相比,本研究记录了虹鳟鱼中TMP的终末消除半衰期长(36.1小时)、稳态分布容积大(5980毫升/千克)和清除率小(2.4毫升/分钟/千克),从而说明了其生物转化和消除能力缓慢,特别是该药物在鳟鱼中的强大“滞留”能力(储存)。4. 本研究中的药代动力学曲线表明,在三种不同的推注剂量(5、10和50毫克/千克)下,TMP不存在剂量依赖性。因此,一级动力学假设得到了验证。5. TMP的尿排泄是鳟鱼中的次要消除途径(剂量的14.4%)。

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