Oral varenicline for smoking cessation.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of varenicline and provide a review of relevant clinical data.

DATA SOURCES: A MEDLINE search (2001-December 2006) was conducted using the key words varenicline and nicotine replacement therapy for clinical trials limited to human subjects and published in English.

STUDY SELECTION AND DATA EXTRACTION: All available human trials of varenicline were selected for review. References cited in identified articles were used for additional citations.

DATA SYNTHESIS: Varenicline selectively targets the alpha4beta2 nicotine receptors in the brain that are responsible for cravings and withdrawal associated with nicotine use and dependence. Maximal plasma concentration occurs within 3-4 hours after administration and, after multiple doses, a steady-state concentration is reached within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is not affected by food or time of administration. It exhibits linear pharmacokinetics and low plasma protein binding (< or =20%) regardless of a patient's age and renal status. It can be administered once daily. Dosage adjustments are not required in patients with hepatic insufficiency, but adjustments may be necessary in patients with severe renal insufficiency. Clinically significant drug-drug interactions have not been observed with varenicline or co-inhibitors of the human organic cation transporter, which mediates renal secretion of varenicline. Substrates such as warfarin, digoxin, cimetidine, metformin, bupropion, and transdermal nicotine do not alter pharmacokinetic parameters when coadministered with varenicline. In vitro studies have not demonstrated alterations in cytochrome P450 enzyme parameters. Varenicline's safety with coadministration of nicotine replacement products has not been well established.

CONCLUSIONS: Varenicline is an effective oral agent for smoking cessation.