Single-dose pharmacokinetics and anticoagulant activity of warfarin is unaffected by nebivolol in healthy volunteers

Abstract

Background Studies have reported that nebivolol possesses distinct nitric oxide releasing/vasodilating properties. The role of nitric oxide on endothelial and platelet function is well established in the literature. Given these actions, the effects of steady-state nebivolol on the pharmacokinetic (PK) and anticoagulant activity of warfarin were studied. Methods This was an open-label study conducted in 12 healthy volunteers. Subjects were given a 10-mg dose of warfarin on Day 1 and Day 17. On Day 8-Day 22, 10 mg oral nebivolol was given QD. Blood samples for assessment of PK and anticoagulation (prothrombin time, INR) were taken at frequent intervals on Day 1 and Day 17. Results Administration of nebivolol resulted in no clinically significant changes in the PK of R- or S-warfarin being observed (see Table). Warfarin protein binding was unaffected by nebivolol. Similarly, nebivolol had no clinically significant effects on the anticoagulant activity of warfarin. Conclusion Once daily dosing of 10 mg nebivolol does not alter the single-dose PK or anticoagulant activity of warfarin. Clinical Pharmacology & Therapeutics (2005) 77, P39–P39; doi: 10.1016/j.clpt.2004.12.043 Table 1. Cmax AUC0-∞ Parameter Ratio 90% CI Ratio 90% CI R-warfarin 1.05 0.95–1.16 1.07 1.03–1.11 S-warfarin 1.09 0.97–1.23 1.10 1.03–1.18