Evaluation of reference-scaled average bioequivalence of two oral formulations ofabiraterone acetate in healthy Chinesesubjects .

Abstract

This study was designed to evaluate the pharmacokinetic (PK) properties and bioequivalence (BE) of two 250-mg tablet formulations of abiraterone acetate: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult Chinese subjects under fasted (n = 40) and fed (n = 40) conditions. The comparison was performed using a single-dose, open, randomized, and four-way replicate study. The concentration of abiraterone in blood samples taken over 48 hours was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). To assess the BE of the test and reference formulations, confidence intervals (CI, 90%) for the peak plasma concentration (Cmax) and area under the concentration-time curves (AUC0-t and AUC0-∞) were calculated using the reference-scaled average bioequivalence (RSABE) method. The results showed that the 90% CIs for the ratios of Cmax, AUC0-t, and AUC0-∞ in the fasted study were 90.14-114.11, 93.96-115.07, and 93.72-113.331, respectively. For the fed study, the 90% CIs were 81.83-102.51, 91.51-104.89, and 91.46-104.58, respectively. In conclusion, the tested 250-mg abiraterone tablets were bioequivalent to 250-mg Zytiga tablets (reference) under both fasted and fed conditions. In addition, food intake increased the systemic exposure and Cmax of abiraterone by 3-fold and 7-fold, respectively. .