Pharmacokinetic comparisons of two different varenicline formulations in humans: Varenicline tartrate versus varenicline oxalate

Background and objective: Varenicline is an effective drug for smoking cessation. The aim of the present study was to compare the pharmacokinetics and safety profiles of two different varenicline formulations (varenicline tartrate (reference) and varenicline oxalate (test)), each containing 1 mg varenicline base in humans. Materials and methods: A randomized, open-label, two-sequence, two-period, single-dose crossover study with a 2-week washout period was conducted with 30 healthy male participants. Blood samples for the pharmacokinetic analysis of varenicline were collected up to 96 hours following the administration of each drug. Pharmacokinetic parameters were also calculated, including the peak plasma concentration (C_max), area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUC_last) as well as AUC from time zero to infinity (AUCinf). ANOVA for pharmacokinetic equivalence was assessed using log-transformed C_max and AUC values, and the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) were assessed as well. The safety profiles were also assessed. Results: 27 participants completed the study. No significant differences were found for any pharmacokinetic parameters of varenicline between the two formulations. The observed average values of C_max, AUC_last, and AUCinf were 4.46 ng/mL, 97.68 ng×h/mL, and 101.60 ng×h/mL for reference and 4.54 ng/mL, 97.10 ng×h/mL, and 100.97 ng×h/mL for test, respectively. The GMRs and 90% CIs for C_max, AUClast, and AUCinf were 1.0106 (0.9626 - 1.0610), 0.9904 (0.9540 - 1.0282), and 0.9885 (0.9517 - 1.0268), respectively. No clinically relevant changes were observed in the physical, biochemical, hematologic, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were found. Conclusion: The results of the present study reveal that varenicline oxalate and varenicline tartrate have similar pharmacokinetic characteristics as varenicline, and that these two formulations exhibit pharmacokinetic equivalence to meet the regulatory criteria. Both varenicline formulations were generally well tolerated.