title: Effect of CYP2C19 polymorphism on the pharmacokinetics of rosuvastatin in healthy Taiwanese subjects.
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 (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.
authors.affiliation: AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Finkelman
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
authors.forename: Tzung-Dau
authors.initials: TD
authors.lastname: Wang
authors.affiliation: Purdue Pharma, Stamford, CT, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA.
authors.forename: Connie T
authors.initials: CT
authors.lastname: Azumaya
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Birmingham
authors.affiliation: AstraZeneca Pharmaceuticals, Mölndal, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Wissmar
authors.affiliation: Covance Inc., Princeton, NJ, USA.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Mosqueda-Garcia
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D044466:Asian People; D001711:Biotransformation; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011110:Polymorphism, Genetic; D011743:Pyrimidines / Q000493:pharmacokinetics; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000493:pharmacokinetics; D013624:Taiwan; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C551067:N-desmethylrosuvastatin; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2C19; pharmacodynamics; pharmacokinetics; polymorphism; rosuvastatin