Abstract
Objective
This study investigated the effect of varenicline on the multiple-dose pharmacokinetics of digoxin.
Methods
Eighteen smokers were randomized to receive digoxin (Lanoxicaps® 0.2 mg QD) with varenicline 1 mg BID or placebo for 14 days.
Results
Varenicline 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.
Conclusion
The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.
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Acknowledgements
The authors thank Anita Tudisco for clinical study management support.
Conflict of interest statement
This study was funded by Pfizer Inc. HM Faessel, AH Burstein, MD Troutman, SA Willavize, KD Rohrbacher, and DJ Clark are full-time employees of Pfizer Global Pharmaceuticals.
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Faessel, H.M., Burstein, A.H., Troutman, M.D. et al. Lack of a pharmacokinetic interaction between a new smoking cessation therapy, varenicline, and digoxin in adult smokers. Eur J Clin Pharmacol 64, 1101–1109 (2008). https://doi.org/10.1007/s00228-008-0530-6
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DOI: https://doi.org/10.1007/s00228-008-0530-6