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

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Abstract
A new method for the investigation of interindividual differenees in drug metabolism is described. We have studied the metabolism of ring-deuterated acetanilid in man following the coadministration of phenaeetin. The principal metabolite of acetanilid-d5 is acetaminophen-d4, and the principal metabolite of phenaeetin is acetaminophen-d0. Using agas chromatograph-mass spectrometer (gc-ms) we are able to monitor both the deuterium-labeled acetaminophen produeed by hydroxylation of acetanilid-d5 and the nonlabeled material produecd 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.