Impact on abiraterone pharmacokinetics and safety: Open-label drug-drug interaction studies with ketoconazole and rifampicin

We evaluated the impact of a strong CYP3A4 inhibitor, ketoconazole, and a strong inducer, rifampicin, on the pharmacokinetic (PK) exposure of abiraterone in two studies in healthy men. All subjects received 1,000 mg of abiraterone acetate on Days 1 and 14. Study A subjects (n = 20) received 400 mg ketoconazole on Days 11–16. Study B subjects (n = 19) received 600 mg rifampicin on Days 8–13. Serial PK sampling was done on Days 1 and 14. Study A: When given with ketoconazole, abiraterone exposure increased by 9% for maximum plasma concentration (Cmax) and 15% for area under the plasma concentration–time curve from 0 to time of the last quantifiable concentration (AUClast) and AUC from time 0 to infinity (AUC∞) compared to abiraterone acetate alone. Study B: When given with rifampicin, abiraterone exposure was reduced to 45% for Cmax and AUC∞ and to 42% for AUClast compared to abiraterone acetate alone. Ketoconazole had no clinically meaningful impact on abiraterone exposure. Rifampicin decreased abiraterone exposure by half. Hence, strong CYP3A4 inducers should be avoided or used with careful evaluation of clinical efficacy when administered with abiraterone acetate.