Associations of the CYP3A5*3 and CYP3A4*1G polymorphisms with the pharmacokinetics of oral midazolam and the urinary 6β‐hydroxycortisol/cortisol ratio as markers of CYP3A activity in healthy male Chinese

摘要: SummaryWhat is known and objective The oral plasma clearance of midazolam the ratio 6β-hydroxycortisol (6β-OHF) to cortisol (F) in urine are two potential markers for evaluating CYP3A activity vivo. We assessed influence common polymorphisms on pharmacokinetics urinary 6β-OHF/F healthy Chinese. Methods Single 15 mg doses were given 20 male Chinese subjects who genotyped CYP3A5*3 CYP3A4*1G polymorphisms. The concentrations determined by LC/MS/MS. Morning samples collected after overnight fasting, F 6β-OHF measured using UPLC. Results discussion There no significant correlations between pharmacokinetic parameters ratios 6β-OHF/F. examined had associations with or midazolam. However, diplotype analysis suggested that CYP3A5 expressers CYP3A4*1/*1G genotype (n = 3) significantly lower AUC0–∞ values (210·0 ± 33·5 vs. 313·9 204·6 h∙ng/mL, P 0·044) higher CL/F (1·16 0·16 0·88 0·48 L/h/kg, 0·005) compared CYP3A4*1/*1 4), which consistent some previous studies tacrolimus. What new conclusion There not associated parameters. possible association their interaction require confirmation a larger study.