Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat.

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±3.4L/h and an apparent volume of distribution at steady state (V ss/F) of 48±23L. The time course of plasma concentrations follows a two-compartment model. The initial half-life (t ½) is approximately 2h and the terminal t ½ determined at daily doses of 40mg or more is 9.4±4.9h. 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 10-240mg, 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.