To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple-dose, 3-period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received febuxostat 80 mg, naproxen 500 mg twice daily, or both. Twenty-four-hour blood samples were collected on day 5 in study 1 and day 7 in study 2. In study 1, 90% confidence intervals of geometric mean ratios for maximum plasma concentration (Cmax) and area under the curve (AUC) were within the 0.80 to 1.25 no-effect range for febuxostat and indomethacin. In study 2, 90% confidence intervals for febuxostat Cmax and AUC extended above that range, with increases of 28% and 40% in Cmax and AUC24, respectively. However, 90% confidence intervals for naproxen Cmax and AUC were within the 0.80 to 1.25 range. Febuxostat had no effect on the plasma pharmacokinetics of indomethacin and naproxen. Similarly, indomethacin had no effect on the plasma pharmacokinetics of febuxostat. Although naproxen caused an increase in plasma exposure to febuxostat, this increase is not expected to be clinically significant. Therefore, based on the plasma pharmacokinetic data in healthy subjects, febuxostat may be administered with indomethacin or naproxen with no dose adjustments for febuxostat, indomethacin, or naproxen.