Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer

Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients.

Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0. 5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety.

Journal of clinical pharmacology. 2015 Jun 10 [Epub ahead of print]

Kim N Chi, Jennifer Spratlin, Christian Kollmannsberger, Scott North, Catherine Pankras, Martha Gonzalez, Apexa Bernard, Hans Stieltjes, Lixian Peng, James Jiao, Milin Acharya, Thian Kheoh, Thomas W Griffin, Margaret K Yu, Caly Chien, Nam Phuong Tran

BC Cancer Agency, Vancouver, BC, Canada. , Cross Cancer Institute, Edmonton, AB, Canada. , BC Cancer Agency, Vancouver, BC, Canada. , Cross Cancer Institute, Edmonton, AB, Canada. , BC Cancer Agency, Vancouver, BC, Canada. , Janssen Research & Development, Raritan, NJ, USA. , Janssen Research & Development, Raritan, NJ, USA. , Janssen Research & Development, Beerse, Belgium. , Janssen Research & Development, Raritan, NJ, USA. , Janssen Research & Development, Raritan, NJ, USA. , Janssen Research & Development, Raritan, NJ, USA. , Janssen Research & Development, San Diego, CA, USA. , Janssen Research & Development, Los Angeles, CA, USA. , Janssen Research & Development, Los Angeles, CA, USA. , Janssen Research & Development, Titusville, NJ, USA. , Janssen Research & Development, Los Angeles, CA, USA.

PubMed