Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers.

Background and Objective: Bupropion is used for the treatment of major depressive disorder. We determined the pharmacokinetics, safety, and tolerability of extended-release bupropion XL in healthy Chinese volunteers.
Methods: This open-label, single-center pharmacokinetic study was conducted between May 2016 and June 2016. Eligible volunteers received bupropion XL 150 mg once daily for 5 days, then 300 mg once daily from days 6 to 14. Pharmacokinetic parameters were evaluated after first and repeated doses by non-compartmental and population pharmacokinetic analyses.
Results: Fifteen out of 16 enrolled volunteers completed the study. The geometric mean of the bupropion area under the concentration-time curve from 0 to 24 h (AUC _0-24 ) was 498.2 and 1,165.7 h·ng/mL on days 1 and 14, respectively; maximum plasma concentration (C _max ) was 49.9 ng/mL on day 1 and steady-state maximum observed plasma concentration (C _ss_max ) was 111.9 ng/mL on day 14. Among the three metabolites, hydroxybupropion showed the highest AUC _0-24 and C _max . The population pharmacokinetic model findings indicated an apparent oral clearance of 221 L/h for bupropion in a typical healthy 60.9-kg Chinese volunteer.
Conclusions: This was the first pharmacokinetic study for bupropion XL and its active metabolites in the Chinese population. The AUC and C _max of bupropion XL and its three metabolites increased approximately in a dose-proportional manner with an increase from 150 mg to 300 mg. Adverse events were similar to those reported in studies outside China. A population pharmacokinetic model was developed for bupropion XL, with pharmacokinetics of bupropion adequately described by a two-compartment model with first-order absorption and linear elimination plus lag time.
Trial Registration Number: NCT02698553.