A phase I, open-label, single-dose, mass balance study of 14C-labeled abiraterone acetate in healthy male subjects.

1. Metabolic disposition of (14)C-abiraterone acetate (AA), a prodrug of abiraterone was assessed in a phase I, open-label, single-dose (1000 mg, approximately 100 μCi) study in healthy males (18-55 years, N = 8). Blood, urine, and faecal samples were obtained at specified timepoints for determination of abiraterone concentrations in the plasma, total radioactivity (TR), and the metabolite profile. 2. Most plasma AA concentrations were below the limit of quantification. The mean maximum plasma concentration (Cmax) of abiraterone was 10.4 ng/mL, mean area under the plasma concentration-time curve (AUC) from 0 to the last measurable plasma concentration (AUC0-last) was 74.8 ng·h/mL. The exposures for TR in plasma (Cmax = 3429 ng·eq/mL; AUC0-last = 26,683 ng eq·h/mL) and whole blood (Cmax = 1836 ng·eq/mL; AUC0-last = 12,162 ng·eq·h/mL) were >300-fold higher than abiraterone exposure in plasma. The majority of TR resided in the plasma compartment of blood. 3. Main circulating metabolites were abiraterone sulfate and N-oxide abiraterone sulfate. The main metabolite excreted in urine was N-oxide abiraterone sulfate (4.22% of TR). Major components of TR in faeces were unchanged AA (55.3% of TR) and abiraterone (22.3% of TR). Mean recovery of TR in faeces was 87.9%, indicating faeces as primary route of excretion.