Acetaminophen production in man after coadministration of acetanilid and phenacetin. A study with stable isotopes

Abstract

A new method for the investigation of interindividual differences in drug metabolism is described. We have studied the metabolism of ring-deuterated acetanilid in man following the coadministration of phenacetin. The principal metabolite of acetanilid-d5 is acetaminophen-d4, and the principal metabolite of phenacetin is acetaminophen-do. Using a gas chromatograph--mass spectrometer (gc-ms) we are able to monitor both the devterion-labeled acetaminophen produced by hydroxylation of acetanilid-d5 and the nonlabeled material produced by oxidative removal of the ethyl group in phenacetin. This system allows us to detect differences in the handling of these drugs by different subjects. nonlabeled material produced by oxidative removal of the ethyl group in phenacetin. This system allows us to detect differences in the handling of these drugs by different subjects.