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

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Abstract

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 (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.

Conclusions

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

NCT02698553

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Acknowledgements

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.

Author information

Author notes

  1. Fan Zhang and Yan Li contributed equally for this manuscript.

Authors and Affiliations

  1. GlaxoSmithKline (China) R&D Company Limited, Shanghai, China

    Fan Zhang, Jingqiu Hu & Jinhua Zhong

  2. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 4/F, 604 Lingling Road, Shanghai, 200030, China

    Yan Li & Huafang Li

  3. Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China

    Yan Li & Huafang Li

Authors
  1. Fan Zhang
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  2. Yan Li
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  4. Jinhua Zhong
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  5. Huafang Li
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Corresponding author

Correspondence to Huafang Li.

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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.

Funding

This study and medical writing assistance was funded by GlaxoSmithKline (China) R&D Company Limited.

Informed consent

Each study volunteer provided written informed consent before any study-specific procedure was performed.

Author Contributions

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.

Data sharing

Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.

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Supplementary material 1 (PDF 191 kb)

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Zhang, F., Li, Y., Hu, J. et al. Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers. Eur J Drug Metab Pharmacokinet 44, 339–352 (2019). https://doi.org/10.1007/s13318-018-0537-z

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  • DOI: https://doi.org/10.1007/s13318-018-0537-z

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