Abstract
Purpose
Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly.
Methods
To overcome the high intra-subject variability of abiraterone, a two-sequence and four-period crossover study was designed to assess bioequivalence between the two products in 32 healthy male Chinese subjects under fasting conditions. The plasma concentration of abiraterone was analyzed by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) assay and the reference-scaled procedure was used to determine bioequivalence for the pharmacokinetics parameters.
Results
The point estimate of geometric mean ratios with 90% confidence interval (CI) of maximum observed concentration (Cmax) and the area under the concentration–time curve (AUC0t) for abiraterone in the test and reference products were 100.19% (90% CI 87.05–115.32%) and 105.99% (90% CI 96.34–116.62%), respectively, and were both within the range of 80.00–125.00%. The 95% confidence upper limit bound for \({({\bar {Y}_{\text{T}}} - {\overline {Y} _{\text{R}}})^{\text{2}}}~ - ~\theta S_{{{\text{WR}}}}^{{\text{2}}}{\text{ }}\) was − 0.1079 for Cmax and was − 0.0515 for AUC0t.
Conclusions
Bioequivalence was demonstrated between the two abiraterone acetate products. The study also confirmed high intra-subject variability, for abiraterone: coefficient of variation (CV, %) of Cmax values for the test and reference products were 40.33% and 46.58%, while for AUC0t were 24.02% and 34.16%, respectively.
Trial registration
http://www.chinadrugtrials.org.cn/: CTR20170997.
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Acknowledgements
This study was supported by Jiangxi Qingfeng Pharmaceutical Co., Ltd. (Jiang Xi, China) and the National Science and Technology Major Project (no. 2017ZX09101001-002-044). The authors would like to thank the study subjects, clinical investigators, study coordinators, CRAs, and the administrative staff at the Xuanwu Hospital who made this study possible.
Funding
This study was supported by Jiangxi Qingfeng Pharmaceutical Co., Ltd. (Jiang Xi, China) and the National Science and Technology Major Project (no. 2017ZX09101001-002-044).
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All the authors have no conflict of interest regarding the sponsor or the content of this article.
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The study protocol, protocol amendments and all applicable documents including informed consent form were reviewed and approved by the Ethic Committee of Xuanwu Hospital Capital Medical University (2017 no. 14).
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Informed consent was obtained from all subjects prior to screening.
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Wang, C., Hu, C., Gao, D. et al. Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Cancer Chemother Pharmacol 83, 509–517 (2019). https://doi.org/10.1007/s00280-018-3754-x
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DOI: https://doi.org/10.1007/s00280-018-3754-x