The Effect of Age and Gender on Pharmacokinetics, Pharmacodynamics, and Safety of Febuxostat, a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase

Abstract

Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase, which is currently being developed for the management of hyperuricemia in patients with gout. The effect of age and gender on the pharmacokinetics, pharmacodynamics, and safety of once-daily oral febuxostat 80 mg was assessed in healthy male and female subjects after 7 days. Following multiple dosing with febuxostat, there were no statistically significant differences in the plasma or urinary pharmacokinetic or pharmacodynamic parameters between subjects aged 18 to 40 years and >or=65 years. Although unbound peak concentration (C(max,u)) and area under the concentration-time curve (AUC(24,u)) for febuxostat were higher in women as compared with men (31.5 vs 23.6 ng/mL, P <or= .01, and 62.8 vs 53.9 ng x h/mL, P <or= .05, for C(max,u) and AUC(24,u), respectively), the differences were not considered clinically significant and could be largely accounted for by weight differences between male and female subjects. For pharmacodynamic parameters, even though the percentage decrease in serum uric acid 24-hour mean concentration was slightly greater in women than in men (59% vs 52%, P <or= .01), this difference was not considered clinically meaningful. Febuxostat was well tolerated in male and female subjects in both age groups. Age or gender had no clinically significant effect on the pharmacokinetics, pharmacodynamics, or safety of febuxostat. Therefore, febuxostat does not require any dose adjustments based on age or gender.