Role of cytochrome P450 isoforms in the metabolism of abamectin and ivermectin in rats

被引：36

作者：

Zeng, ZP

Andrew, NW

Woda, JM

Halley, BA

Crouch, LS

Wang, RW

机构：

[1] Merck Research Laboratories, Rahway, NJ 07065

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 1996年 / 44卷 / 10期

关键词：

avermectin; ivermectin; metabolism; rat; cytochrome P450; isoform;

D O I：

10.1021/jf960222+

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

Abamectin (AVM) and ivermectin (IVM) are each metabolized by rat liver microsomes to 3 ''-O-desmethyl(3 ''-ODMe), 24-hydroxymethyl (24-OHMe), and 26-hydroxymethyl (26-OHMe) derivatives. Microsomes from rats pretreated with dexamethasone(Dex), but not 3-methylcholanthrene (3MC), increased the formation of 3 ''-ODMe metabolites of both AVM and IVM. Troleandomycin inhibited formation of 3 ''-ODMe metabolites by >80% by microsomes from Dex-induced rats. Therefore, cytochrome P450 3A plays a major role in this metabolic pathway. Formation of the 26-OHMe metabolites was markedly increased by microsomes from SMC-treated but not Dex-treated rats. Formation of 24-OHMe from AVM, but not IVM, was slightly increased by microsomes from 3MC-treated rats. Consistent with this observation, anti-rat cytochrome P450 1Al inhibited formation of 26-OHMe metabolites of AVM and IVM by 90 and 40%, respectively. This antibody also inhibited formation of the 24-OHMe metabolite from AVM by 60% but not from IVM. Thus, cytochrome P450 1A1 is involved in the hydroxylation of the 26-methyl group of both AVM and IVM as well as the 24-methyl group of AVM but not the 24-methyl group of IVM.

引用

页码：3374 / 3378

页数：5

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