title: Pharmacokinetics and pharmacodynamics of single-dose oral tolvaptan in fasted and non-fasted states in healthy Caucasian and Japanese male subjects.
abstract: OBJECTIVE
  To compare the pharmacokinetics and pharmacodynamics of tolvaptan in Caucasian and Japanese healthy male subjects under fasting and non-fasting conditions.
  
  
  METHODS
  This was a single-center, parallel-group, randomized, open-label, three-period crossover trial of single oral doses of tolvaptan 30 mg under fasting and non-fasting [a high-fat, high-calorie meal (HFM) or Japanese standard meal] conditions in 25 healthy male Caucasian subjects and 24 healthy male Japanese subjects. Pharmacodynamic endpoints were urine volume and fluid balance for 0 to 24 h postdose.
  
  
  RESULTS
  In the fasted state, the plasma tolvaptan C(max) and AUC(∞) geometric mean ratios (90 % confidence interval) were 1.105 (0.845-1.444) and 1.145 (0.843-1.554) for Japanese compared to Caucasian subjects. A HFM increased the C(max) and AUC(∞) values by about 1.15-fold in both Japanese and Caucasian subjects.. Twenty-four-hour urine volumes paralleled pharmacokinetic changes, but the increases were not clinically significant. Fluid balance in the Japanese men was 1.4- to 2.0-fold more negative than that in the Caucasian men.
  
  
  CONCLUSIONS
  Tolvaptan pharmacokinetics is not clinically significantly affected by race. Body weight is a factor that affects exposure. Tolvaptan can be administered with or without food.
authors.affiliation: Clinical Pharmacology, Otsuka Pharmaceutical Development & Commercialization, Inc, 2440 Research Blvd., Rockville, MD, 20850, USA. susan.shoaf@otsuka-us.com
authors.forename: Susan E
authors.initials: SE
authors.lastname: Shoaf
authors.forename: Seong Ryul
authors.initials: SR
authors.lastname: Kim
authors.forename: Patricia
authors.initials: P
authors.lastname: Bricmont
authors.forename: Suresh
authors.initials: S
authors.lastname: Mallikaarjun
mesh_terms: D000284:Administration, Oral; D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D044466:Asian People; D001552:Benzazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005215:Fasting / Q000378:metabolism*; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077602:Tolvaptan; D014556:Urine; D044465:White People; D055815:Young Adult
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan