Drug-Drug Interaction Study to Assess the Effects of Multiple-Dose Pitavastatin on Steady-State Warfarin in Healthy Adult Volunteers
| Autor: | Masahiko Gosho, Yoichiro Inagaki, Bill Arana, Roger E. Morgan, Thomas Hunt |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Pharmacology Young Adult Therapeutic index Pharmacokinetics medicine Humans Drug Interactions heterocyclic compounds Pharmacology (medical) International Normalized Ratio cardiovascular diseases Pitavastatin CYP2C9 Clotting factor Prothrombin time Cross-Over Studies Dose-Response Relationship Drug medicine.diagnostic_test business.industry Warfarin Pharmacodynamics Quinolines Drug Therapy Combination business Follow-Up Studies medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 51:1302-1309 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270010379811 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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