Published in:
01-01-2015 | Original Article
Pharmacokinetics of abiraterone in healthy Japanese men: dose-proportionality and effect of food timing
Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2015
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Purpose
Abiraterone acetate (AA) was recently approved for castration-resistant prostate cancer in Japan. Two phase 1 studies were conducted to assess the pharmacokinetics of abiraterone after single-dose administration in Japanese healthy men and to evaluate the effects of food timing on abiraterone pharmacokinetics after single-dose administration of AA in Japanese and Caucasian healthy men.
Methods
In the dose-proportionality study, subjects (n = 30 Japanese) were randomly assigned to receive single doses of 250, 500, and 1,000 mg AA, and in the food-timing study, subjects (n = 22 Japanese and n = 23 Caucasian) randomly received single doses of 1,000 mg AA under fasted (overnight) and three different modified fasting conditions.
Results
Mean C
max and AUC∞ for abiraterone increased dose-dependently in Japanese healthy men; however, 90 % confidential interval (CI) was outside the predefined dose-proportionality criteria. Based on geometric mean ratios and 90 % CIs (versus overnight fasting condition), abiraterone exposure (AUC) increased significantly with dosing 1 h premeal, 2 h postmeal, or in between two meals 4 h apart by 57 %, 595 %, and 649 %, respectively.
Conclusion
No clinically meaningful difference was observed in the pharmacokinetics of abiraterone between Caucasian and Japanese subjects.