No interaction between nebivolol and digoxin in healthy volunteers

Background Nebivolol is a new generation cardiovascular agent reported to have vasodilating actions owing to its ability to potentiate nitric oxide release from the endothelium coupled with highly cardioselective β1-adrenergic antagonism. It has been studied worldwide in a variety of disorders such as hypertension, CHF and angina. As concomitant administration of nebivolol with digoxin is likely to occur when nebivolol becomes commercially available, the effect of nebivolol on the pharmacokinetics (PK) of digoxin was assessed in 13 healthy volunteers. Methods Subjects received a 0.25 mg oral loading dose of digoxin BID on Day 1 followed by QD on Days 2–17. On Days 8–17, subjects also received a QD dose of 10 mg nebivolol. Blood samples for PK assessment of digoxin were taken at frequent intervals on Days 7 and 17. Results Administration of nebivolol resulted in no clinically significant changes in the PK of digoxin (Cmax: Ratio 1.07, 90% CI 0.94–1.21; AUC0–24hr: Ratio 1.08, 90% CI 1.03–1.14). Moreover, there was no evidence of any cardiovascular or laboratory test result abnormalities. Conclusions No clinically significant changes in the PK of digoxin were observed with the co-administration of nebivolol. Therefore, no dose adjustments are considered necessary for digoxin when given concomitantly with nebivolol. Clinical Pharmacology & Therapeutics (2005) 77, P76–P76; doi: 10.1016/j.clpt.2004.12.183