Diazepam metabolism in native Chinese poor and extensive hydroxylators of S-mephenytoin: Interethnic differences in comparison with white subjects

Abstract

A single oral 5 mg dose of diazepam was given to 16 healthy native Chinese Han volunteers. Eight volunteers were extensive metabolizers of S-mephenytoin, and eight were poor metabolizers of S-mephenytoin. Plasma levels of diazepam and its demethyl metabolite were determined by HPLC in blood samples drawn during 4 weeks. There was no difference in diazepam disposition between the two phenotypes. However, the plasma half-life of demethyldiazepam was longer in poor metabolizers than in extensive metabolizers of mephenytoin (mean +/- SD: 161 +/- 37 and 116 +/- 29 hours, respectively; p less than 0.02). The plasma concentrations of demethyldiazepam at 7, 14, and 21 days after intake of diazepam were significantly higher in poor metabolizers than in extensive metabolizers. We compared the pharmacokinetic parameters of diazepam in Chinese subjects with our previously reported data from white subjects. The mean plasma half-life values of diazepam in Chinese extensive metabolizers (85.1 hours) and poor metabolizers (88.3 hours) were very similar to those in white subjects who were poor metabolizers (88.3 hours), and more than twice those in white subjects who were extensive metabolizers (40.8 hours). In parallel, the mean clearance of diazepam in Chinese subjects (independent of phenotype) was similar to that in white subjects who were poor metabolizers, but half that in white subjects who were extensive metabolizers. Chinese subjects had a slightly larger volume of distribution of diazepam than white subjects.(ABSTRACT TRUNCATED AT 250 WORDS)