Effects of a single administration of 6-aminonicotinamide on hepatic microsomal drug metabolism in rats

Abstract

Pretreatment of rats with 6-aminonicotinamide (6-AN) induced a significant increase in aminopyrine (AM) N-demethylation and hexobarbital (HX) hydroxylation in rats. In this study, the concentrations of AM, 4-monomethylaminoantipyrine (MAA), aminoantipyrine (AA) and further metabolites were measured by using the GC/MS method. The increase in AM N-demethylation induced by 6-AN treatment was confirmed by measuring the area under the plasma concentration-time curve (AUC) for AM, MAA and AA in rats after AM administration. Of the first two steps of AM metabolism mediated by cytochrome P-450-coupled monooxygenase, the second step (from MAA to MA) was found to be more affected by 6-AN than the first one (from AM to MAA).