HUMAN AND MOUSE-LIVER COUMARIN 7-HYDROXYLASES DO NOT METABOLIZE WARFARIN INVITRO

被引：6

作者：

HONKAKOSKI, P

ARVELA, P

JUVONEN, R

LANG, MA

KAIRALUOMA, M

PELKONEN, O

机构：

[1] UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND

[2] OULU UNIV,CENT HOSP,DEPT SURG,SF-90220 OULU,FINLAND

[3] UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND

来源：

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 1992年 / 33卷 / 03期

关键词：

WARFARIN; COUMARIN; HYDROXYLATION; P450; 2A6; 2A-5; DRUG METABOLISM;

D O I：

10.1111/j.1365-2125.1992.tb04042.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 The contribution of human P450 2A6 and mouse P450 2a-5 isoenzymes, both highly active in coumarin 7-hydroxylation, to the metabolism of warfarin was studied in several in vitro systems with human and mouse liver preparations. 2 The reconstituted P450 2a-5 purified from DBA/2 mouse liver did not metabolize warfarin. 3 An anti-P450 2a-5 antibody did not consistently inhibit any of the warfarin biotransformation reactions catalyzed by human or mouse liver microsomes, although coumarin 7-hydroxylation was inhibited by over 90%. 4 In some human microsomal samples, 4- and 8-hydroxylations of warfarin were inhibited to some extent by the anti-P450 2a-5 antibody. 5 Warfarin (< 1 mM) did not inhibit coumarin 7-hydroxylation by human or mouse liver microsomes in vitro. 6 We conclude that mouse and human coumarin 7-hydroxylases do not oxidise warfarin.

引用

页码：313 / 317

页数：5

共 21 条

[1] SIMPLE AND SENSITIVE ASSAY OF 7-ETHOXYCOUMARIN DEETHYLATION [J].