Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers

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 (C_max) and the area under the concentration–time curve (AUC_0t) 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 \({({\bar {Y}_{\text{T}}} - {\overline {Y} _{\text{R}}})^{\text{2}}}~ - ~\theta S_}}^}{\text{ }}\) was − 0.1079 for C_max and was − 0.0515 for AUC_0t.

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 C_max values for the test and reference products were 40.33% and 46.58%, while for AUC_0t were 24.02% and 34.16%, respectively.

Trial registration

http://www.chinadrugtrials.org.cn/: CTR20170997.

https://ift.tt/2QkgQfY