Lack of a pharmacokinetic interaction between a new smoking cessation therapy,varenicline, and digoxin in adult smokers |
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| Authors: | H. M. Faessel A. H. Burstein M. D. Troutman S. A. Willavize K. D. Rohrbacher D. J. Clark |
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| Affiliation: | (1) Department of Neuroscience Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA;(2) Department of Clinical Research Operations, Pfizer Global Research and Development, New London, CT 06320, USA;(3) Department of Pharmacokinetics, Dynamics and Metabolism, ADME Technology Group, Pfizer Global Research and Development, New London, CT 06320, USA;(4) Department of Statistics, Pfizer Global Research and Development, New London, CT 06320, USA;(5) Department of Clinical Pharmacology, Clinical Assay Group, Pfizer Global Research and Development, New London, CT 06320, USA;(6) Department of Neuroscience, Pfizer Global Research and Development, New London, CT 06320, USA |
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| Abstract: | ObjectiveThis study investigated the effect of varenicline on the multiple-dose pharmacokinetics of digoxin.MethodsEighteen smokers were randomized to receive digoxin (Lanoxicaps® 0.2 mg QD) with varenicline 1 mg BID or placebo for 14 days.ResultsVarenicline had no clinically relevant effect on the digoxin steady-state exposure, as evidenced by the 90% confidence intervals for the ratios of AUC0–24 (87.5–108%) and Cmin (83.8–116%) wholly contained within 80–125%. Digoxin Cmax and Tmax remained unchanged in the presence of varenicline, consistent with no apparent alteration in digoxin bioavailability. A minimal 11.3% increase in digoxin renal clearance was noted during varenicline treatment while having no impact on its systemic exposure. Results are supported by mechanistic evidence in Caco-2 cell monolayers that varenicline is neither a P-gp substrate nor an inhibitor of P-gp-mediated efflux of digoxin. Co-administration of varenicline and digoxin was well tolerated.ConclusionThe results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment. |
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| Keywords: | Smoking cessation Varenicline Drug-drug interaction Digoxin |
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