Effect of CYP2C19 polymorphism on the pharmacokinetics of rosuvastatin in healthy Taiwanese subjects.

CYP2C19 contributes to N-desmethyl rosuvastatin formation in "in vitro" models. Approximately 80% of Taiwanese are CYP2C19 extensive metabolizers (EMs, CYP2C19*1/*1, *1/*2, or *1/*3). We studied the potential effect of CYP2C19 genotypes on rosuvastatin pharmacokinetics in healthy Taiwanese subjects following single and multiple daily oral doses of rosuvastatin calcium (20 mg). Geometric mean ratios for poor metabolizers (PMs): EMs for rosuvastatin were 0.974 and 0.872 for area under the curve and maximum plasma concentration on day 1 (1.01 and 0.965 on day 17) and for N-desmethyl rosuvastatin, 1.21 and 1.07 on day 1 (1.14 and 1.09 on day 17), respectively. Changes of lipid profiles from baseline to day 18 for PMs and EMs were -52.4% and -53.3% (low-density lipoprotein cholesterol), and -34.2% and -30.0% (total cholesterol), respectively. Rosuvastatin was generally well-tolerated by both PMs and EMs. These results suggest that CYP2C19 polymorphism does not affect rosuvastatin pharmacokinetics in healthy Taiwanese in a clinically meaningful way.