title: Drug-drug interaction study to assess the effects of multiple-dose pitavastatin on steady-state warfarin in healthy adult volunteers.
abstract: Warfarin, an antagonist of vitamin K, which inhibits clotting factor synthesis, is prescribed for thrombosis prophylaxis and treatment and is known to have a narrow therapeutic range. Pitavastatin is a potent HMG-CoA reductase inhibitor. In this study, the influence of multiple-dose pitavastatin (4 mg once daily) on steady-state warfarin pharmacodynamic and pharmacokinetic profiles was investigated in 24 healthy male participants whose international normalized ratio (INR) was maintained by individualized doses of warfarin. The ratio of the least squares mean of prothrombin time and INR was 0.989 (90% confidence interval [CI], 0.955-1.023) and 0.993 (0.956-1.209), respectively (test: warfarin + pitavastatin; reference: warfarin only). The geometric mean ratios of C(max) and AUC were 1.034 (90% CI, 0.994-1.075) and 1.066 (1.035-1.099), respectively, for R-warfarin and 1.033 (0.995-1.073) and 1.058 (1.026-1.092), respectively, for S-warfarin. Warfarin pharmacodynamic profiles and pharmacokinetic profiles did not differ between the warfarin monotherapy and the coadministration of pitavastatin and warfarin. No drug-drug interaction between pitavastatin and warfarin was demonstrated.
authors.affiliation: Kowa Research Institute, 430 Davis Drive, Suite 200, Morrisville, NC 27560, USA. y-inagak@kowa.co.jp
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Thomas
authors.initials: T
authors.lastname: Hunt
authors.forename: Bill
authors.initials: B
authors.lastname: Arana
authors.forename: Masahiko
authors.initials: M
authors.lastname: Gosho
authors.forename: Roger
authors.initials: R
authors.lastname: Morgan
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D011804:Quinolines; D014859:Warfarin; C108475:pitavastatin