Microsomal acyl glucuronidation: enzyme-kinetic studies with labile glucuronides

Abstract

Because of the labile nature of acyl glucuronides under physiologic conditions, metabolic rates of formation calculated using traditional methods may be confounded by concomitant rates of degradation. True metabolic formation rates may be approximated by stabilization of the metabolic product or by purifying the metabolite and calculating its degradation rate under similar conditions to that utilized in the formation experiments. This latter degradation rate is used to correct the apparent formation parameter in the absence of inhibitors. The advantages and limitations of each approach are reviewed employing studies to characterize rates of acyl glucuronidation for nonsteroidal antiinflammatory drugs.