An integrated population pharmacokinetic model of febuxostat in pediatric patients with hyperuricemia including gout and adult population of healthy subjects and patients with renal dysfunction.

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The study objective was to validate febuxostat dosage and administration in pediatric patients with hyperuricemia including gout, using an integrated population pharmacokinetic (PopPK) analysis in the Japanese population. Integrated PopPK analysis of febuxostat used a nonlinear mixed-effects modeling (NONMEM) program on plasma febuxostat concentration data for 2611 samples from Japanese pediatric patients with hyperuricemia including gout (n = 29) and from adult subjects who are healthy or have renal dysfunction (n = 113). We described febuxostat pharmacokinetics using an integrated PopPK model applicable both to pediatric patients and to the adult population. The covariates of body weight and eGFR were identified for CL/F and the covariate of fasted/fed status for bioavailability. The range of steady-state exposures (Cmax,ss and AUCτ,ss) for 5, 10, 20, and 30 mg of febuxostat in fed pediatric patients weighing 20 to 40 kg was within that for 10, 20, 40, and 60 mg of febuxostat in fed pediatric patients and adults weighing 40 to 120 kg. Post hoc estimates of CL/F, adjusted by body weight, differed little between pediatric patients and the adult population in the renal function categories of normal, mild dysfunction, and moderate dysfunction. We successfully validated the febuxostat dose that provided the same level of exposure in pediatric patients as in the adult population: half the adult dose for pediatric patients weighing <40 kg and the full adult dose for pediatric patients weighing ≥40 kg. As in adults, the results support the use of febuxostat without dose adjustment in pediatric patients who have mild to moderate renal dysfunction.