Pharmacokinetics and Bioequivalence Study of Varenicline Tartrate in Healthy Chinese Subjects

OBJECTIVE  To evaluate the bioequivalence of the test and reference formulations of varenicline tartrate in healthy Chinese subjects under fasting and fed conditions.

METHODS  This study employed a single-center, randomized, open-label, single-dose, two-period, two-sequence crossover design. A total of 24 subjects were enrolled in each group(fasting and fed), and each subject received a 1 mg dose of either the test or reference formulation in each period. Varenicline plasma concentrations were measured using LC-MS/MS, and pharmacokinetic parameters were calculated using WinNonlin 8.1 software to assess bioequivalence.

RESULTS  In the fasting group, the pharmacokinetic parameters of the test and reference formulations were as follows: C_max (5.73±1.23) ng·mL⁻¹ vs (5.47±1.05) ng·mL⁻¹, AUC_0-t (107.57±17.70) h·ng·mL⁻¹ vs (111.78±25.29) h·ng·mL⁻¹, AUC_0-∞ (111.48±18.87) h·ng·mL⁻¹ vs (116.33±27.74) h·ng·mL⁻¹, T_max 1.50 h vs 1.50 h, t_1/2 (20.37±4.14) h vs (20.23±3.81) h. In the fed group, the pharmacokinetic parameters for the test and reference formulations were: C_max (5.88±1.02) ng·mL⁻¹ vs (6.26±1.13) ng·mL⁻¹, AUC_0-t (107.72±19.15) h·ng·mL⁻¹ vs (114.24±27.11) h·ng·mL⁻¹, AUC_0-∞ (119.52±30.10) h·ng·mL⁻¹ vs (112.04±20.75) h·ng·mL⁻¹, T_max 2.00 h vs 2.00 h, t_1/2 (21.39±3.79) h vs (22.19±4.50) h. The average bioequivalence method indicated that the 90% confidence intervals(CIs) for C_max, AUC_0−t, and AUC_0−∞ under fasting conditions were 97.88%−111.60%, 92.33%−103.60%, and 91.92%−103.61%, respectively. Under fed conditions, the corresponding CIs were 87.63%−101.74%, 88.63%−104.53%, and 88.05%−104.31%, all within the acceptable range of 80%−125%.

CONCLUSION  The test formulation of varenicline tartrate is bioequivalent to the reference formulation under both fasting and fed conditions.