Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study.
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Feng B, Obach RS, Burstein AH, Clark DJ, de Morais SM, Faessel HM
Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study.
Clin Pharmacol Ther. 2008 Apr;83(4):567-76. doi: 10.1038/sj.clpt.6100405. Epub 2007 Oct 31.
- PubMed ID
- 17971819 [ View in PubMed]
- Abstract
Varenicline is predominantly eliminated unchanged in urine, and active tubular secretion partially contributes to its renal elimination. Transporter inhibition assays using human embryonic kidney 293 cells transfected with human renal transporters demonstrated that high concentrations of varenicline inhibited substrate uptake by hOCT2 (IC(50)=890 microM), with very weak or no measurable interactions with the other transporters hOAT1, hOAT3, hOCTN1, and hOCTN2. Varenicline was characterized as a moderate-affinity substrate for hOCT2 (K(m)=370 microM) and its hOCT2-mediated uptake was partially inhibited by cimetidine. Co-administration of cimetidine (1,200 mg/day) reduced the renal clearance of varenicline in 12 smokers, resulting in a 29.0% (90% CI: 21.5%-36.9%) increase in systemic exposure. This increase is not considered clinically relevant, as it should not give rise to safety concerns. Consequently, it can be reasonably expected that other inhibitors of hOCT2 would not cause greater renal interactions with varenicline than that seen with the efficient hOCT2 inhibitor cimetidine.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Varenicline Solute carrier family 22 member 2 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareVareniclineCholine The excretion of Varenicline can be decreased when combined with Choline. VareniclineThiamine The excretion of Varenicline can be decreased when combined with Thiamine. VareniclineRanolazine The excretion of Varenicline can be decreased when combined with Ranolazine. VareniclineMetoprolol The excretion of Varenicline can be decreased when combined with Metoprolol. VareniclineDisopyramide The excretion of Varenicline can be decreased when combined with Disopyramide.