title: Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.
abstract: The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment.
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Hira
authors.forename: Yugo
authors.initials: Y
authors.lastname: Chisaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noda
authors.forename: Hisazumi
authors.initials: H
authors.lastname: Araki
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yano
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Morita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069465:Febuxostat / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006074:Gout Suppressants / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D006074:Gout Suppressants; D000069465:Febuxostat