Key result
Nebivolol 10 mg daily does not alter warfarin pharmacokinetics or anticoagulant activity.
Why the study?
The effects of steady-state nebivolol on the pharmacokinetics and anticoagulant activity of warfarin were studied due to nebivolol's nitric oxide releasing and vasodilating properties.
Does nebivolol alter the pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers?
Does nebivolol alter the pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers?
Effect estimate: Ratio 1.10 (95% CI 1.03-1.18)
Nebivolol 10 mg daily does not significantly alter the pharmacokinetics or anticoagulant activity of a single dose of warfarin in healthy volunteers.
No PK or anticoagulant interaction in healthy volunteers; leaves open effects during chronic warfarin use in patients.
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 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
No takes yet. Share an insight, caveat, or question.
Lawrence et al. (2005) studied healthy volunteers (n=12). nebivolol vs. warfarin alone was evaluated on pharmacokinetics (AUC0-∞) of S-warfarin (Ratio 1.10, 95% CI 1.03-1.18). Once daily dosing of 10 mg nebivolol does not clinically significantly alter the single-dose pharmacokinetics (S-warfarin AUC ratio 1.10; 90% CI 1.03-1.18) or anticoagulant activity of warfarin.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: