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

Abstract

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. This open-label, single-center pharmacokinetic study was conducted between May 2016 and June 2016. Eligible volunteers received bupropion XL 150mg once daily for 5days, then 300mg once daily from days 6 to 14. Pharmacokinetic parameters were evaluated after first and repeated doses by non-compartmental and population pharmacokinetic analyses. Fifteen out of 16 enrolled volunteers completed the study. The geometric mean of the bupropion area under the concentration-time curve from 0to 24h (AUC0-24) was 498.2 and 1,165.7h·ng/mL on days 1 and 14, respectively; maximum plasma concentration (Cmax) was 49.9ng/mL on day 1 and steady-state maximum observed plasma concentration (Css_max) was 111.9ng/mL on day 14. Among the three metabolites, hydroxybupropion showed the highest AUC0-24 and Cmax. 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. This was the first pharmacokinetic study for bupropion XL and its active metabolites in the Chinese population. The AUC and Cmax of bupropion XL and its three metabolites increased approximately in a dose-proportional manner with an increase from 150mg to 300mg. 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. NCT02698553.