title: Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy East Asian Subjects.
abstract: OBJECTIVE
  The objective of these studies was to evaluate the pharmacokinetic profile, safety, and tolerability of mirabegron, a β3-adrenoceptor agonist for the treatment of overactive bladder, including food effects (low- or high-fat meals) and sex, in healthy East Asian subjects.
  
  
  METHODS
  In total, 5 pharmacokinetic studies of mirabegron were conducted in healthy East Asian subjects. Food effects were assessed in 3 randomized, single-dose studies in young Japanese male subjects (study 1), male and female subjects (study 2), and young Taiwanese male and female subjects (study 3). In the other 2 single- and multiple-dose studies in young Chinese male and female subjects (study 4 and study 5), mirabegron was administered as a single dose under fasted conditions. After the washout period, mirabegron was administered once daily under fed conditions for 8 days. Pharmacokinetic parameters were determined using noncompartmental methods. Safety and tolerability assessments included physical examinations, vital signs, 12-lead ECG, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event monitoring.
  
  
  RESULTS
  After administration of single oral doses of mirabegron, exposure under fed conditions was lower than under fasted conditions in Japanese and Taiwanese subjects. In Japanese subjects, a greater reduction in mirabegron Cmax and AUC0-∞ was observed after a low-fat meal compared with a high-fat meal. In Chinese subjects, Cmax was reached at approximately 4.0 hours after single oral doses. Mirabegron accumulated 2- to 3-fold on once-daily dosing of multiple-dose relative to single-dose data. Steady state was reached within 7 days. After administration of mirabegron, mean values for Cmax and AUC in female subjects were higher than those in male subjects. Mirabegron was well tolerated in Japanese, Taiwanese, and Chinese subjects.
  
  
  CONCLUSIONS
  Our studies confirm the higher exposure levels of mirabegron in female compared with male East Asian subjects as found earlier in Western subjects. Furthermore, the effects of food on the pharmacokinetic profiles appeared to be similar among the 3 populations tested in our studies. The findings suggest that there are no significant pharmacokinetic differences among the Japanese, Taiwanese, and Chinese populations.
authors: Global Project Management, Astellas Pharma Inc, Tokyo, Japan. Electronic address: hiromi.iitsuka@astellas.com.
authors: Hiromi
authors: H
authors: Iitsuka
authors: Global Clinical Pharmacology, Astellas Pharma Global Development, Leiden, the Netherlands.
authors: Marcel
authors: M
authors: van Gelderen
authors: Clinical Pharmacology, Astellas Pharma Inc, Tokyo, Japan.
authors: Masataka
authors: M
authors: Katashima
authors: Clinical Pharmacology, Astellas Pharma Inc, Tokyo, Japan.
authors: Shin
authors: S
authors: Takusagawa
authors: Clinical Pharmacology, Astellas Pharma Inc, Tokyo, Japan.
authors: Taiji
authors: T
authors: Sawamoto
mesh_terms: D000083:Acetanilides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000284:Administration, Oral; D058667:Adrenergic beta-3 Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000706:statistics & numerical data; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D012737:Sex Factors; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000208:ethnology / Q000378:metabolism*; D064804:Urological Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D013844:Thiazoles; D064804:Urological Agents; C520025:mirabegron
keywords: East Asia; Ethnic difference; healthy volunteers; mirabegron; pharmacokinetics