You could be reading the full-text of this article now if you...

If you have access to this article through your institution,
you can view this article in

The Effect of Aleglitazar on the Pharmacokinetics and Pharmacodynamics of S- and R-Warfarin in Healthy Male Subjects

Sanwald-Ducray, Patricia PharmD, PhD; Jamois, Candice PharmD; Banken, Ludger PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0000000000000033
Original Article
Abstract

Abstract: Aleglitazar acts through balanced activation of peroxisome proliferator–activated receptors α and γ; warfarin is a commonly prescribed anticoagulant. Given the extent of cardiovascular disease in patients with type 2 diabetes, cotreatment with aleglitazar and warfarin is likely in this population. This open-label, randomized, 2-period, crossover study in 12 healthy male subjects investigated the potential for drug–drug interactions between warfarin and aleglitazar (final data drawn from 11 white subjects). The primary objective was to investigate the effect of aleglitazar on the pharmacokinetic properties of S-warfarin and on the pharmacodynamics of the racemic mixture; the secondary objectives included the effect of aleglitazar on R-warfarin pharmacokinetics and of racemic warfarin on aleglitazar pharmacokinetics. Subjects were randomized to single-dose warfarin on day 1 or aleglitazar once daily (12 days) plus single-dose warfarin on day 6 followed by a 14-day washout period, then crossover. Coadministration of aleglitazar reduced S- and R-warfarin exposure (AUC0–∞) by 18% and 13%, respectively, but did not change its pharmacodynamic effects (prothrombin time and factor VII activity). After warfarin dosing, aleglitazar trough concentrations remained within the same range. These findings indicate that coadministration of aleglitazar and warfarin is unlikely to affect the efficacy or safety of either agent.

Author Information

Department of Clinical Pharmacology, pRED Development, F. Hoffmann-La Roche AG, Basel, Switzerland.

Reprints: Patricia Sanwald-Ducray, PharmD, PhD, Clinical Pharmacology, pRED Development, F. Hoffmann-La Roche AG, Bldg/Room 663/2130, Postfach, Basel 4070, Switzerland (e-mail: patricia.sanwald_ducray@roche.com).

Supported by F. Hoffmann-La Roche AG.

All authors are employees of F. Hoffmann-La Roche AG.

Received July 02, 2013

Accepted October 11, 2013

© 2014 by Lippincott Williams & Wilkins.