Triazolam pharmacokinetics and pharmacodynamics in Caucasians and Southern Asians: ethnicity and CYP3A activity

Abstract

A threefold higher area under the plasma drug concentration-time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians when compared with Caucasians. To determine if these differences are specific to nifedipine or apply to other substrates of CYP3A, we examined the pharmacokinetics and pharmacodynamics of 0.375 mg triazolam, another substrate of CYP3A, in eight healthy Caucasians and eight healthy Southern Asians in a double-blind placebo-controlled study. When compared with Caucasians, Southern Asians achieved higher maximum plasma concentration (C_max) (8.0±2.6 vs 4.8±1.9 ng ml^-1; the 95% confidence interval (CI) of the mean difference was 0.76 to 5.7; P max) (45 min (range 30–75) vs 90 min (range 60–145); the 95% CI of the mean difference was -69 to -20; P vs 1138.9±1182.4; the 95% CI of the mean difference was -1897.2 to - 34.4; P vs 1086.0±827.1; the 95% CI of the mean difference was -1564.2 to -175.6; P = 0.02; double stance:eyes closed (DSEC): 207.5±89.8 vs 1156.9±932.1; the 95% CI of the mean difference was - 1718.5 to -178.5; P = 0.02; with no significant difference between the two ethnic groups. These results suggest that the large inter-ethnic difference in nifedipine clearance are not generalizable to all CYP3A4 substrates.