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Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 5/2017

17.10.2016 | Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat

verfasst von: Bishoy Kamel, Garry G. Graham, Kenneth M. Williams, Kevin D. Pile, Richard O. Day

Erschienen in: Clinical Pharmacokinetics | Ausgabe 5/2017

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Abstract

Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.4 L/h and an apparent volume of distribution at steady state (V ss/F) of 48 ± 23 L. The time course of plasma concentrations follows a two-compartment model. The initial half-life (t ½) is approximately 2 h and the terminal t ½ determined at daily doses of 40 mg or more is 9.4 ± 4.9 h. Febuxostat is administered once daily. The maximum (peak) plasma concentrations are approximately 100-fold greater than the trough concentrations. Consequently, there is no significant accumulation of the drug during multiple dose administration. There are few data on the pharmacokinetics of febuxostat in patients with gout. While the pharmacokinetic parameters are not affected by mild to moderate hepatic impairment, there is no consensus on whether renal impairment has any effect on the pharmacokinetics of febuxostat. Febuxostat is extensively metabolised by oxidation (approximately 35 %) and acyl glucuronidation (up to 40 %); febuxostat acyl glucuronides are cleared by the kidney. In healthy subjects treated with multiple doses of febuxostat 10–240 mg, the concentrations of serum urate are reduced by a maximum of about 80 %. The percentage reduction in the concentrations of serum urate is slightly less in gouty patients than in healthy subjects.
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Metadaten
Titel
Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat
verfasst von
Bishoy Kamel
Garry G. Graham
Kenneth M. Williams
Kevin D. Pile
Richard O. Day
Publikationsdatum
17.10.2016
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 5/2017
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-016-0466-4

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