Effect of CYP2C19 polymorphism on the pharmacokinetics of rosuvastatin in healthy Taiwanese subjects
Journal
Clinical Pharmacology in Drug Development
Journal Volume
4
Journal Issue
1
Pages
33-40
Date Issued
2015
Author(s)
Abstract
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 (20mg). 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. ? 2014, The American College of Clinical Pharmacology.
Subjects
CYP2C19; Pharmacodynamics; Pharmacokinetics; Polymorphism; Rosuvastatin
Other Subjects
cytochrome P450 2C19; drug metabolite; high density lipoprotein cholesterol; low density lipoprotein cholesterol; n methyl rosuvastin; rosuvastatin; rosuvastatin lactone; triacylglycerol; unclassified drug; CYP2C19 protein, human; cytochrome P450 2C19; hydroxymethylglutaryl coenzyme A reductase inhibitor; N-desmethylrosuvastatin; pyrimidine derivative; rosuvastatin; sulfonamide; adult; aged; area under the curve; Article; clinical trial; constipation; controlled study; CYP2C19 gene; DNA polymorphism; dose response; drug accumulation; drug blood level; drug clearance; drug distribution; drug metabolism; drug safety; drug tolerability; female; genotype; human; human experiment; lipid composition; male; maximum plasma concentration; myalgia; normal human; pharmacogenetics; repeated drug dose; single drug dose; Taiwanese; time to maximum plasma concentration; Asian continental ancestry group; biotransformation; blood; drug administration; genetic polymorphism; genetics; metabolism; middle aged; oral drug administration; pharmacogenetic testing; pharmacogenetic variant; phenotype; Taiwan; young adult; Administration, Oral; Adult; Aged; Area Under Curve; Asian Continental Ancestry Group; Biotransformation; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Female; Genotype; Healthy Volunteers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Phenotype; Polymorphism, Genetic; Pyrimidines; Rosuvastatin Calcium; Sulfonamides; Taiwan; Young Adult
Publisher
Blackwell Publishing Ltd
Type
journal article