Formation of 2-sulphamoylacetylphenol from zonisamide under aerobic conditions in rat liver microsomes

被引：11

作者：

Nakasa, H ^{[1
]}

Ohmori, S ^{[1
]}

Kitada, M ^{[1
]}

机构：

[1] CHIBA UNIV HOSP,DIV PHARM,CHUO KU,CHIBA 260,JAPAN

来源：

XENOBIOTICA | 1996年 / 26卷 / 05期

关键词：

D O I：

10.3109/00498259609046727

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The antiepileptic agent zonisamide, 1,2-benzisoxazole-3-methanesulphonamide, was metabolized reductively to 2-sulphamoyl-acetylphenol (SMAP) not only under anaerobic conditions but also under aerobic conditions in liver microsomes of rat pretreated with phenobarbital or dexamethasone. 2. NADPH was required for the formation of SMAP from zonisamide under aerobic conditions. In addition, the reductive metabolism of zonisamide under these conditions was substantially inhibited by carbon monoxide, ketoconazole, and cimetidine, known inhibitors of cytochrome P450. 3. The formation of SMAP under aerobic conditions in liver microsomes was increased by pretreatment of rat with triacetyloleandomycin (TAO) and was increased by the treatment of the microsomes with ferricyanide. 4. These results imply that zonisamide is metabolized reductively to SMAP by a cytochrome P450 belonging to the 3A subfamily under aerobic conditions as well as anaerobic conditions.

引用

页码：495 / 501

页数：7

共 25 条

[1]

ARCHAKOV AI, 1989, BASIS MECHANISMS REG, P151

[2] DUAL EFFECTS OF MACROLIDE ANTIBIOTICS ON RAT-LIVER CYTOCHROME-P-450 - INDUCTION AND FORMATION OF METABOLITE-COMPLEXES - A STRUCTURE-ACTIVITY RELATIONSHIP [J].