Improved determination of drug metabolism by perifusion of recombinant V79 cells carrying human CYP3A4

被引：8

作者：

Gebhardt, R ^{[1
]}

Lippert, C

Schneider, A

Doehmer, J

机构：

[1] Univ Tubingen, Inst Physiol Chem, D-72076 Tubingen, Germany

[2] Univ Klinikum, Inst Biochem, D-04103 Leipzig, Germany

[3] TU Munchen, Inst Toxikol & Umwelthyg, D-80636 Munich, Germany

来源：

TOXICOLOGY IN VITRO | 1999年 / 13卷 / 4-5期

关键词：

cytochrome P450; drug metabolism; perifusion; testosterone; recombinant cell lines; V79; cells;

D O I：

10.1016/S0887-2333(99)00020-X

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Recombinant V79Mz cell lines stably co-expressing human CYP3A4 and human NADPH-cytochrome P450 oxidoreductase were used to compare testosterone metabolism under conventional stationary cultivation and under perifusion. In contrast to stationary culture. steady-state conditions for the production of 6 beta-hydoxytestosterone were established in the perifusion system even when different concentrations of testosterone were infused sequentially. As a consequence of these favourable conditions, threefold higher maximal metabolic rates could be measured and kinetic constants could be determined more reproducibly than in stationary culture. The results indicate that CYP3A4 shows an autocatalytic reaction kinetic probably due to two binding sites Tor testosterone. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：639 / 643

页数：5

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