Lack of a pharmacokinetic interaction between a new smoking cessation therapy, varenicline, and digoxin in adult smokers.
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 AUC(0-24) (87.5-108%) and C(min) (83.8-116%) wholly contained within 80-125%. Digoxin C(max) and T(max) 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.


CONCLUSIONS
The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.
Faessel
H M
HM
Department of Neuroscience Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA. helene.m.faessel@pfizer.com
Burstein
A H
AH
Troutman
M D
MD
Willavize
S A
SA
Rohrbacher
K D
KD
Clark
D J
DJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001552:Benzazepines / Q000494:pharmacology*; D018938:Caco-2 Cells; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011810:Quinoxalines / Q000494:pharmacology*; D016540:Smoking Cessation; D000068580:Varenicline
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001552:Benzazepines; D011810:Quinoxalines; D004077:Digoxin; D000068580:Varenicline