Steady-state pharmacodynamics and pharmacokinetics of warfarin in the presence and absence of telmisartan in healthy male volunteers.

ABSTRACT

The effects of multiple-dose telmisartan on the steady-state pharmacodynamics and pharmacokinetics of warfarin were assessed in 12 healthy young males in an open-label, single-period study conducted over 30 days. Subjects received loading doses of oral once-daily warfarin on days 1 to 5, which were individually adjusted at days 6 and/or 9 to attain stable predose prothrombin time values (INRpre) of between 1.2 and 1.8 by the end of medication phase 1 (day 14). From days 15 to 24 (medication phase 2), subjects received oral once-daily telmisartan 120 mg in addition to individualized oral doses of once-daily warfarin. On days 25 to 31 (medication phase 3), oral once-daily warfarin was again administered alone at individualized doses. Under steady-state conditions, INRpre remained unchanged during medication phases 1, 2, and 3. The difference between phases 1 and 3 was -0.04 (95% confidence interval [CI] -0.7 to 0.10) and between phases 2 and 1 was 0.03 (95% CI -0.11 to 0.10). Mean trough plasma warfarin concentrations (Cpre) were stable during medication with warfarin alone but showed a small, although statistically significant, decrease during the combined-medication phase. The point estimate of the ratio of phase 2/phase 1 was 0.89 (95% CI 0.84 to 0.95). The decrease in Cpre did not result in decreased anticoagulation. This suggests that the extent of pharmacokinetic interaction between telmisartan and warfarin is limited, and since telmisartan had no effect on INRpre and the concomitant medication was well tolerated, there is no evidence for a clinically relevant interaction between telmisartan and warfarin.