Lack of a pharmacokinetic interaction between a new smoking cessation therapy, varenicline, and digoxin in adult smokers

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Abstract
This study investigated the effect of varenicline on the multiple-dose pharmacokinetics of digoxin. Eighteen smokers were randomized to receive digoxin (Lanoxicaps® 0.2 mg QD) with varenicline 1 mg BID or placebo for 14 days. 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. The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.

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