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8-甲氧基补骨脂素在犬体内的药代动力学

Pharmacokinetics of 8-methoxypsoralen in the dog.

作者信息

Monbaliu J G, Belpaire F M, Braeckman R A, Bogaert M G

机构信息

Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.

出版信息

Biopharm Drug Dispos. 1988 Jan-Feb;9(1):9-17. doi: 10.1002/bod.2510090103.

Abstract

The pharmacokinetics of 8-MOP were studied in six dogs following intravenous administration of 2 mg kg-1. In most animals a bi-exponential decline of the plasma level profile was observed. The calculated pharmacokinetic parameters varied considerably between the different dogs. The mean half-lives of distribution and of elimination were 0.20 and 2.17 h, respectively. The average total plasma clearance was 0.51 l kg-1 h-. Following both oral and intravenous administration of doses of 1, 3, and 10 mg kg-1, non-linear kinetics were found. Non-linearity was confirmed following administration of the substance at increasing infusion rates. Finally in four dogs, extraction by the liver was calculated by measuring 8-MOP concentration in the femoral artery and in a hepatic vein after intravenous administration of 1 mg kg-1. The extraction varied from animal to animal (18 per cent to nearly 100 per cent). Administration of an additional dose of 3 mg kg-1 in two of the dogs led to a decreased extraction.

摘要

在6只犬静脉注射2mg/kg体重的8-甲氧基补骨脂素后,对其药代动力学进行了研究。在大多数动物中,观察到血浆水平曲线呈双指数下降。不同犬之间计算得到的药代动力学参数差异很大。分布半衰期和消除半衰期的平均值分别为0.20小时和2.17小时。平均总血浆清除率为0.51L/kg体重·小时。口服和静脉注射1、3和10mg/kg体重剂量后,均发现非线性动力学。在以递增输注速率给药后,证实了非线性。最后,在4只犬中,静脉注射1mg/kg体重后,通过测量股动脉和肝静脉中8-甲氧基补骨脂素的浓度来计算肝脏的摄取率。摄取率因动物而异(18%至近100%)。在其中2只犬中额外给予3mg/kg体重的剂量导致摄取率降低。

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