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[使用人类肝脏活检样本作为评估细胞色素P-450的技术]

[Use of human liver biopsy samples as a technique for evaluation of cytochrome P-450].

作者信息

Isa M

机构信息

Lab. de chimie Pharmaceutique, Ecole de Pharmacie, Université Catholique de Louvain, Bruxelles, Belgique.

出版信息

J Pharm Belg. 1996 Jul-Aug;51(4):189-91.

PMID:8965248
Abstract

Liver cytochromes-P450 are of primary importance in the metabolism of numerous drugs. Their activity is modulated by exogenous factors such as drug treatment. The parameters of human oxidase metabolism were determined "in vitro" in order to evaluate the activity of a specific monooxygenase (benzopyrene hydroxylase). Substances capable of modulating monooxygenase function were identified. This may be useful to predict drug-Cyt-P450 interaction "in vivo". The hydroxylation of benzopyrene in human microsomes prepared from human liver samples (biopsies) was used as a model to study the treatment effect on cytochrome-P450. The kinetic parameters of this reaction are stable and reproducible (Km = 1.37 +/- 0.35 microM, Vmax = 0.49 +/- 0.03 nmole 30 H-BP/min/ nmole CYT-P450). The Michaelis-Menten values are given by mean +/- standard deviation.

摘要

肝脏细胞色素P450在众多药物的代谢中至关重要。它们的活性受到诸如药物治疗等外源性因素的调节。为了评估一种特定单加氧酶(苯并芘羟化酶)的活性,在“体外”测定了人类氧化酶代谢的参数。确定了能够调节单加氧酶功能的物质。这对于预测“体内”药物与细胞色素P450的相互作用可能是有用的。用人肝脏样本(活检)制备的人微粒体中苯并芘的羟化作用作为模型来研究治疗对细胞色素P450的影响。该反应的动力学参数稳定且可重复(米氏常数Km = 1.37 +/- 0.35微摩尔,最大反应速率Vmax = 0.49 +/- 0.03纳摩尔30分钟内每纳摩尔细胞色素P450代谢的苯并芘量)。米氏-门坦值以平均值 +/- 标准差给出。

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