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The distribution and gender difference of CYP3A activity in Chinese subjects
Bing Zhu1, Zhao-Qian Liu, Guo-Lin Chen
1Pharmacogenetics Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan 410078, China.
Aims:
To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity.
Methods:
Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1'-hydroxymidazolam:midazolam (1'-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1'-OH-MDZ and MDZ in plasma were measured by HPLC RESULTS: A 13-fold variation of CYP3A activity (log1'-OH-MDZ:MDZ: range -0.949-0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov-Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05).
Conclusions:
A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle.