title: A repeated oral administration study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with impaired renal function in Japan: pharmacokinetic and pharmacodynamic study.
abstract: BACKGROUND
  Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative.
  
  
  OBJECTIVE
  A multicenter, open-label, parallel, between-group comparative study was conducted to investigate the effects of renal function on the pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel inhibitor of uric acid synthesis.
  
  
  METHODS
  Based on creatinine clearance (Ccr), 29 subjects were assigned to 3 groups: normal renal function (Ccr ≥ 80 mL/min), mild renal dysfunction (80 mL/min > Ccr ≥ 50 mL/min), or moderate renal dysfunction (50 mL/min > Ccr ≥ 30 mL/min). Febuxostat was repeatedly orally administered at a dose of 20 mg/d for 7 days.
  
  
  RESULTS
  Impaired renal function caused a slight increase in systemic exposure to unchanged febuxostat and its oxidative metabolites, but the exposure did not increase through repeated administration. Moreover, renal impairment did not markedly reduce the effects of febuxostat on plasma uric acid levels. There were no clinically significant adverse events even in patients with impaired renal function.
  
  
  CONCLUSIONS
  Febuxostat is considered an inhibitor of uric acid synthesis that could be used in patients with mild to moderate renal impairment without dose adjustment.
authors.affiliation: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi Minato-ku, Tokyo, Japan. t-hosoya@jikei.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Hosoya
authors.initials: H
authors.lastname: Tatsuo
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohno
authors.forename: Ohno
authors.initials: O
authors.lastname: Iwao
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D000069465:Febuxostat; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006074:Gout Suppressants / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010117:Oxypurinol / Q000652:urine; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000097:blood*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000097:blood; D055815:Young Adult
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D014969:Xanthine Oxidase; D010117:Oxypurinol