Bioequivalence Evaluation of Generic Febuxostat versus Feburic ® in Healthy Chinese Subjects: A Randomized Crossover Study

Purpose Febuxostat, a xanthine oxidase inhibitor, is a first-line treatment for gout with hyperuricemia. This study evaluated the pharmacokinetic (PK) bioequivalence, safety profile, and food effects of a generic febuxostat formulation compared to the reference product (Feburic®) in healthy Chinese volunteers Patients and Methods In this randomized, open-label, two-sequence, two-period crossover trial, 80 participants (74 males, 6 females) received single 40 mg doses of both test and reference formulations under fasting and fed conditions, separated by a 7-day washout. Plasma concentrations were quantified using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Primary endpoints included peak plasma concentration (C _max ), area under the plasma concentration-time curve from time zero to the last time quantifiable time point (AUC _0 − t ), and area under the plasma concentration-time curve from time zero to infinity (AUC _0−∞ ), with bioequivalence determined using 90% confidence intervals (CIs) for geometric mean ratios (GMRs). Results All 90% CIs for GMRs fell within the 80–125% bioequivalence range (fasting: AUC _0 − t 99.08-104.28%, AUC _0−∞ 98.73-103.84%, C _max 92.87-112.14%; fed: AUC _0 − t 101.16-106.21%, AUC _0−∞ 101.13-105.94%, C _max 91.72-105.07%). High-fat meals delayed T _max by 0.67 h ( P  < 0.05) and reduced systemic exposure (C _max by ~ 35%, AUC _0−∞ by ~ 12%). Adverse event incidence was 12.8% (fasting) and 25.0% (fed), with no serious adverse events reported. Conclusion The generic febuxostat formulation demonstrated PK equivalence to Feburic® under both fasting and fed conditions, with comparable safety profiles. The observed food effects, while statistically significant, support flexible administration without meal restrictions, positioning this generic as a clinically equivalent, cost-effective alternative for gout management. Clinical Trial Registration: This study was prospectively registered (Registration No. CTR20233483; First Public Release Date: 1 November 2023) in the Chinese Clinical Trial Registration Platform (http://www.chinadrugtrials.org.cn), a registry recognized by the Chinese National Medical Products Administration (NMPA). The trial was conducted from 28 November 2023 to 26 December 2023.