Evaluation of the Pharmacokinetics of Abiraterone Acetate and Abiraterone Following Single-Dose Administration of Abiraterone Acetate to Healthy Subjects.

Background And Objective: Following oral administration of abiraterone acetate, the parent compound abiraterone acetate is rapidly metabolized to abiraterone. To our knowledge, bioanalytical methods to date have not been able to detect the parent compound in human plasma, and bioassay was only performed on the metabolite. A highly sensitive bioanalytical method was developed and validated to measure plasma concentrations of the parent compound. In this study, both analytes were assayed and used to evaluate the full pharmacokinetic profile of abiraterone acetate tablets.

Methods: This was an open-label, single-dose, one-period, one-treatment, pharmacokinetic study performed in 18 healthy subjects. Each subject was administered four tablets (corresponding to a total dose of 1000 mg) of abiraterone acetate. Blood samples for pharmacokinetic analysis were collected up to 60 h post-dose. Subjects' plasma concentrations for abiraterone acetate were assayed using highly sensitive validated bioanalytical methods with a lower limit of quantitation (LLOQ) of 0.5 pg/ml for abiraterone acetate and 0.1 ng/ml for abiraterone. Safety assessments were performed throughout the study.

Results: The pharmacokinetic results for abiraterone acetate showed a mean for the maximum plasma concentration (C) of 54.67 ± 68.30 pg/ml, and a median time to maximum concentrations (t) of 5.53 h (range 2.67-35.00 h). The means for area under the concentration-time curve (AUC) from time 0 h to infinity (AUC) and AUC from time zero h to the time of the last measurable abiraterone acetate concentrations (AUC) were 386.13 ± 266.80 pg·h/ml and 460.07 ± 378.78 pg·h/ml, respectively. The apparent elimination half-life (t) showed a mean of 8.98 ± 3.92 h. None of the adverse events that affected three subjects (16.7%) were related to the study drug.

Conclusion: The ability to detect the low plasma abiraterone acetate concentrations, in addition to abiraterone, resulted in a complete characterization of the pharmacokinetics of abiraterone acetate that was not possible with other analytical methods that only measured the metabolite. The development of new bioanalytical methods such as these will allow for a more thorough understanding of the pharmacokinetics of abiraterone acetate, and this, in turn, can have an impact on both future examinations into abiraterone acetate pharmacokinetic behaviour and the evaluation of its generic formulations.