THE INFLUENCE OF ETHNIC FACTORS AND GENDER ON CYP1A2-MEDIATED DRUG DISPOSITION - A COMPARATIVE-STUDY IN CAUCASIAN AND CHINESE SUBJECTS USING PHENACETIN AS A MARKER SUBSTRATE

To assess potential ethnic and gender-related differences in the expre ssion of cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2 substrate) and its metabolite paracetamol were co mpared in 20 Caucasian and 20 Chinese subjects after administration of a single oral 900 mg phenacetin dose. Peak plasma concentrations and apparent oral clearance values for phenacetin did not differ between t he two groups (geometric means: 3.4 mu g/ml and 1.56 ml h(-1) kg(-1), respectively, for Caucasians vs. 4.7 mu g/ml and 1.25 ml h(-1) kg(-1), respectively, for Chinese, after excluding one Caucasian with aberran tly low plasma phenacetin values). Pharmacokinetic parameters for meta bolically derived paracetamol were also similar in the two groups. Whe n subjects were divided into subgroups according to gender, phenacetin apparent oral clearance values were found to be lower in Chinese wome n compared with both Chinese men and Caucasian subjects of either sex. It is concluded that there are no major interethnic differences in th e expression of CYP1A2-related activity between Caucasians and Chinese , although Chinese women as a subgroup may exhibit comparatively lower enzyme activity.