Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers
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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.
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.
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 (AUC0–24) was 498.2 and 1,165.7 h·ng/mL on days 1 and 14, respectively; maximum plasma concentration (Cmax) was 49.9 ng/mL on day 1 and steady-state maximum observed plasma concentration (Css_max) was 111.9 ng/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 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
The authors thank all the study participants and trial site staff who were involved in the conduct of this trial. The authors also thank Yucheng Sheng (GSK), for calculating AUC0-∞ for bupropion after single-dose administration of 150 mg and 300 mg through simulation, and Pravin Bolshete (TATA Consultancy Services, India), for providing medical writing assistance.
Compliance with ethical standards
Conflicts of interest
Fan Zhang, Jingqiu Hu, and Jinhua Zhong were employees of GSK while conducting the study and during manuscript development. The remaining authors have no conflict of interest to declare.
This study and medical writing assistance was funded by GlaxoSmithKline (China) R&D Company Limited.
Each study volunteer provided written informed consent before any study-specific procedure was performed.
All authors participated in the conception or study design and data interpretation. YL and HL also helped in acquisition of data. All the authors participated in drafting the manuscript, and read, revised and approved the final manuscript for submission.
Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.
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