Zp. Zeng et al., ROLE OF CYTOCHROME-P450 ISOFORMS IN THE METABOLISM OF ABAMECTIN AND IVERMECTIN IN RATS, Journal of agricultural and food chemistry, 44(10), 1996, pp. 3374-3378
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 pre
treated with dexamethasone(Dex), but not 3-methylcholanthrene (3MC), i
ncreased the formation of 3 ''-ODMe metabolites of both AVM and IVM. T
roleandomycin 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 metab
olites was markedly increased by microsomes from SMC-treated but not D
ex-treated rats. Formation of 24-OHMe from AVM, but not IVM, was sligh
tly increased by microsomes from 3MC-treated rats. Consistent with thi
s observation, anti-rat cytochrome P450 1Al inhibited formation of 26-
OHMe metabolites of AVM and IVM by 90 and 40%, respectively. This anti
body also inhibited formation of the 24-OHMe metabolite from AVM by 60
% but not from IVM. Thus, cytochrome P450 1A1 is involved in the hydro
xylation 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.