Effect of pitavastatin vs. rosuvastatin on international normalized ratio in healthy volunteers on steady-state warfarin.
Curr Med Res Opin. 2011 Dec 8;
Authors: Yu CY, Campbell SE, Zhu B, Pat Knadler M, Small DS, Sponseller CA, Hunt TL, Morgan RE
Abstract
ABSTRACT Objective: Statins have been shown to impact international normalized ratio (INR) when coadministered with warfarin. The aim of this study was to assess the effect of pitavastatin compared with rosuvastatin on steady-state pharmacodynamics (PD) of warfarin by measuring INR in healthy adult subjects. Methods: Subjects received oral doses of warfarin 5?mg once daily on days?1 through 3. The dose was titrated on days?4 through 9 to reach a steady-state INR of 1.5 to 2.2. Warfarin was continued on days?10 through 21and pitavastatin 4?mg or rosuvastatin 40?mg was administered once daily on days 14 through 22. After a 14-day washout period, the process was repeated with the alternate statin. Results: For pitavastatin, mean INR changed from 1.73±0.18 (n?=?42) on day 14 before starting statin dosing, to 1.78±0.29 (n?=?42) on day 22 at treatment end; the difference in INR was not significant (p?=?0.219). For rosuvastatin, mean INR increased significantly from 1.74±0.20 (n?=?43) at baseline to 1.90±0.30 (n?=?43) at treatment end (p?<?0.001). Rosuvastatin caused a significantly greater increase in INR than pitavastatin (p?<?0.001). Conclusion: Steady-state INR during warfarin treatment did not change significantly when pitavastatin 4 mg was added to the regimen, while a significant increase was observed when rosuvastatin 40 mg was added. The effect of rosuvastatin on INR was significantly larger than the effect of pitavastatin. This study is limited because it was done in healthy volunteers. Further studies in patient populations are needed to better understand the clinical significance of the results.
PMID: 22149769 [PubMed - as supplied by publisher]