Muraglitazar does not alter the pharmacokinetics and pharmacodynamics of concomitantly administered warfarin in healthy subjects

Background Muraglitazar (MURA) is a novel PPAR α/γ dual agonist. This oxybenzylglycine analog (nonthiazolidinedione) reduces glucose and lipid levels in patients with type 2 diabetes. These patients may be on warfarin, which is commonly prescribed but susceptible to alterations in its pharmacokinetics (PK) and pharmacodynamics (PD) by medications administered concomitantly. We assessed the potential of MURA to affect the PK and PD of WAR. Methods This was an open-label, sequential study involving 16 healthy subjects. In period 1, PK and PD effects of single-dose administration of 25mg WAR were evaluated. In period 2, MURA 10mg was administered daily for 10 days with assessment of MURA PK on days 7 and 8. PK and PD effects of MURA+WAR were evaluated on day 8 after another single dose of 25mg WAR. Results The geometric mean (%CV) Cmax of S and R warfarin was 1732 (20) and 1719 (18), and with MURA, 1668 (18) and 1643 (17) ng/mL. The geometric mean (%CV) AUC(INF) of S and R warfarin was 53757 (40) and 88679 (38), and with MURA, 49981 (32) and 88463 (30) ng·h/mL. Concomitant MUR+WAR was well tolerated with no major bleeding-related AEs. Conclusion MURA had no significant effect on PK/PD of WAR based on Cmax, AUC(INF), max INR, and AUC(INR). WAR did not alter steady state PK of MURA. Study results support co-administration of WAR and MURA. Clinical Pharmacology & Therapeutics (2005) 77, P81–P81; doi: 10.1016/j.clpt.2004.12.201