Food Enhanced Pharmacokinetics for Clinical Translation of Low Dose Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer
Author(s): Meenakshi Meenu, Ranjit Kumar Sahoo, Amlesh Seth, Ujjalkumar Das, Thirumurthy Velpandian, Dharamvir Singh Arya
Introduction: Abiraterone acetate (AAc) is prescribed in metastatic castration-resistant prostate cancer (mCRPC) with recommendation to administer in fasted state due to food-drug interaction. This study was designed to compare pharmacokinetics of 250 mg AAc in fed state with 1000 mg in fasted state for use of low dose AAc as a cost-effective alternative.
Patients and Methods: A randomized, open label, nonreplicated crossover clinical study was conducted after ethics approval and trial registration. Eighteen patients were randomized into two groups: 1. Test- 250 mg AAc in fed state (milk, 7% fat); 2. Reference-1000 mg AAc in fasted state. Drug was administered for 6 days and on 7th day, blood samples were withdrawn at predose, 1, 2, 3, 4 and 6 hours. Patients were crossed-over to other groups and process was repeated. Abiraterone levels in plasma were estimated using liquid chromatography–mass spectrometry. Maximum (Cmax) and minimum (Cmin) plasma concentrations, area under curve from 0 to 6 hours (AUC0- 6) were estimated and appropriate statistical tests were applied.
Results: Seventeen mCRPC patients completed the study. Difference in mean Cmax between test (107.86 ng/mL) and reference (88.71 ng/mL) was not statistically significant (p>0.05) so was the difference in mean AUC0-6 (p>0.05). Trough plasma concentrations had statistically significant (p<0.05) difference between test (4.3 ng/mL) and reference (7.5 ng/mL) but were above known half-maximal inhibitory concentration of abiraterone (1.4 ng/mL) in both groups. Conclusion: AAc 250 mg with milk had similar pharmacokinetics with 1000 mg in fasted state and, is a cost-effective alternative.