Comparison of pharmacokinetics and uric acid lowering effect between two different strength febuxostat formulations (80 mg vs. 40 mg) in healthy subjects.

Abstract

Febuxostat is a selective inhibitor of xanthine oxidase, which is used to manage hyperuricemia in patients with gout. The objective of the study was to compare the pharmacokinetics of two different strength of febuxostat formulations (80 mg and 40 mg). A randomized, single-dose, open-label, two-period, two-sequence crossover study with a 7-day washout period was conducted in 30 healthy male subjects. Participants received either reference (1 — 80 mg) or test (2 — 40 mg) formulations during the first period and the alternative formulation during the second period. Plasma samples for the drug analysis were collected up to 24 hours after treatment. All pharmacokinetic parameters were comparable between the two formulations The observed mean Cmax, AUC(last), and AUC(∞) values for the reference formulation were 3,670 ng/mL, 12,086 ng x h/mL, and 12,880 ng x h/mL, respectively. Corresponding values for the test formulation were 4,108 ng/mL, 12,689 ng x h/mL, and 13,278 ng x h/mL, respectively. The geometric mean ratios (90% CI) between the two formulations were 1.1273 (1.0286 - 1.2355) for Cmax, 1.054 (1.0115 - 1.0980) for AUC(last), and 1.0395 (0.9959 - 1.0851) for AUC(∞). The changes of serum uric acid at 24 hours after reference and test formations were comparable (-1.36 mg/dL for reference and -1.37 mg/dL for test; p = 0.892). The results of the present study indicated that the reference and test formulations have comparable pharmacokinetics and that these two formulations meet the regulatory criteria for bioequivalence. In addition, the reduction of serum UA levels in the reference formulation was similar to that of the test formulation after a single dose.