title: Lack of a pharmacokinetic interaction between a new smoking cessation therapy, varenicline, and digoxin in adult smokers.
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 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.
authors.affiliation: Department of Neuroscience Clinical Pharmacology, Pfizer Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA. helene.m.faessel@pfizer.com
authors.forename: H M
authors.initials: HM
authors.lastname: Faessel
authors.forename: A H
authors.initials: AH
authors.lastname: Burstein
authors.forename: M D
authors.initials: MD
authors.lastname: Troutman
authors.forename: S A
authors.initials: SA
authors.lastname: Willavize
authors.forename: K D
authors.initials: KD
authors.lastname: Rohrbacher
authors.forename: D J
authors.initials: DJ
authors.lastname: Clark
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001552:Benzazepines; D011810:Quinoxalines; D004077:Digoxin; D000068580:Varenicline