title: Pharmacokinetics of abiraterone in healthy Japanese men: dose-proportionality and effect of food timing.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  No clinically meaningful difference was observed in the pharmacokinetics of abiraterone between Caucasian and Japanese subjects.
authors.affiliation: Janssen Pharmaceutical, KK, Tokyo, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Akira
authors.initials: A
authors.lastname: Shishido
authors.forename: Nicole
authors.initials: N
authors.lastname: Vaccaro
authors.forename: James
authors.initials: J
authors.lastname: Jiao
authors.forename: Hans
authors.initials: H
authors.lastname: Stieltjes
authors.forename: Apexa
authors.initials: A
authors.lastname: Bernard
authors.forename: Margaret
authors.initials: M
authors.lastname: Yu
authors.forename: Caly
authors.initials: C
authors.lastname: Chien
mesh_terms: D000328:Adult; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000069501:Abiraterone Acetate; D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001213:Asian; D018592:Cross-Over Studies; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions / Q000208:ethnology; D006207:Half-Life; D007564:Japan / Q000208:ethnology; D062407:Meals; D008657:Metabolic Clearance Rate; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000208:ethnology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013607:Tablets; D014481:United States; D044465:White People
chemical_list: D000069501:Abiraterone Acetate; D000736:Androstenes; D018931:Antineoplastic Agents, Hormonal; D065607:Cytochrome P-450 Enzyme Inhibitors; D013254:Steroid 17-alpha-Hydroxylase; D013607:Tablets