Warfarin Pharmacodynamics Unaffected by Cilomilast

OBJECTIVE:To demonstrate a lack of effect of steady-state concentrations of cilomilast, a new oral phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease, on warfarin-induced anticoagulation.METHODS:This 28–day, randomized, double-blind, placebo-controlled, parallel-group study involved 36 healthy men. All volunteers received warfarin once daily on days 1 through 24 of the study. After a standard 5–mg loading dose on days 1 and 2, the warfarin dose was titrated between days 3 and 10 to achieve a stable prothrombin time, expressed as international normalized ratio (INR). Volunteers received either cilomilast 15 mg twice daily or placebo on days 18 through 24. The primary end point was the INR on day 24.RESULTS:On day 24, the mean ± SEM INR in subjects receiving concurrent warfarin and cilomilast was 1.35 ± 0.05, compared with 1.38 ± 0.07 in those receiving concurrent warfarin and placebo. The point estimate (90% CI) for the difference in day 24 INR values between cilomilas...