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.
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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.
Authors: Emmy Boerrigter; Guillemette E Benoist; Joanneke K Overbeek; Rogier Donders; Niven Mehra; Inge M van Oort; Rob Ter Heine; Nielka P van Erp Journal: Br J Clin Pharmacol Date: 2021-10-08 Impact factor: 3.716
Authors: Guillemette E Benoist; Rianne J Hendriks; Peter F A Mulders; Winald R Gerritsen; Diederik M Somford; Jack A Schalken; Inge M van Oort; David M Burger; Nielka P van Erp Journal: Clin Pharmacokinet Date: 2016-11 Impact factor: 6.447
Authors: E David Crawford; Neal D Shore; Daniel P Petrylak; Celestia S Higano; Charles J Ryan Journal: Ther Adv Med Oncol Date: 2017-03-22 Impact factor: 8.168