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. CONCLUSION: The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.
RCT Entities:
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. CONCLUSION: The results suggest that digoxin can be safely administered with varenicline without the need for dose adjustment.
Authors: J Stangier; C A Su; M G Hendriks; J J van Lier; F A Sollie; B Oosterhuis; J H Jonkman Journal: J Clin Pharmacol Date: 2000-12 Impact factor: 3.126
Authors: R A Boyd; R H Stern; B H Stewart; X Wu; E L Reyner; E A Zegarac; E J Randinitis; L Whitfield Journal: J Clin Pharmacol Date: 2000-01 Impact factor: 3.126
Authors: Douglas E Jorenby; J Taylor Hays; Nancy A Rigotti; Salomon Azoulay; Eric J Watsky; Kathryn E Williams; Clare B Billing; Jason Gong; Karen R Reeves Journal: JAMA Date: 2006-07-05 Impact factor: 56.272
Authors: Jotham W Coe; Paige R Brooks; Michael G Vetelino; Michael C Wirtz; Eric P Arnold; Jianhua Huang; Steven B Sands; Thomas I Davis; Lorraine A Lebel; Carol B Fox; Alka Shrikhande; James H Heym; Eric Schaeffer; Hans Rollema; Yi Lu; Robert S Mansbach; Leslie K Chambers; Charles C Rovetti; David W Schulz; F David Tingley; Brian T O'Neill Journal: J Med Chem Date: 2005-05-19 Impact factor: 7.446
Authors: H Rollema; L K Chambers; J W Coe; J Glowa; R S Hurst; L A Lebel; Y Lu; R S Mansbach; R J Mather; C C Rovetti; S B Sands; E Schaeffer; D W Schulz; F D Tingley; K E Williams Journal: Neuropharmacology Date: 2006-12-08 Impact factor: 5.250
Authors: Aaron H Burstein; David J Clark; Melissa O'Gorman; Susan A Willavize; Timothy G Brayman; G Scott Grover; Robert L Walsky; R Scott Obach; Hélène M Faessel Journal: J Clin Pharmacol Date: 2007-11 Impact factor: 3.126
Authors: Hélène M Faessel; R Scott Obach; Hans Rollema; Patanjali Ravva; Kathryn E Williams; Aaron H Burstein Journal: Clin Pharmacokinet Date: 2010-12 Impact factor: 6.447
Authors: Christopher J Magnus; Peter H Lee; Jordi Bonaventura; Roland Zemla; Juan L Gomez; Melissa H Ramirez; Xing Hu; Adriana Galvan; Jayeeta Basu; Michael Michaelides; Scott M Sternson Journal: Science Date: 2019-03-14 Impact factor: 47.728