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Purpose <p>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<sup>®</sup>) in healthy Chinese volunteers</p> Patients and methods <p>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<sub>max</sub>), area under the plasma concentration-time curve from time zero to the last time quantifiable time point (AUC<sub>0-t</sub>), and area under the plasma concentration-time curve from time zero to infinity (AUC<sub>0-∞</sub>), with bioequivalence determined using 90% confidence intervals (CIs) for geometric mean ratios (GMRs).</p> Results <p>All 90% CIs for GMRs fell within the 80–125% bioequivalence range (fasting: AUC<sub>0-t</sub> 99.08–104.28%, AUC<sub>0-∞</sub> 98.73–103.84%, C<sub>max</sub> 92.87–112.14%; fed: AUC<sub>0-t</sub> 101.16–106.21%, AUC<sub>0-∞</sub> 101.13–105.94%, C<sub>max</sub> 91.72–105.07%). High-fat meals delayed T<sub>max</sub> by 0.67 h and Tlag by 0.37 h (<i>p</i> &lt; 0.05) while reducing systemic exposure (C<sub>max</sub> by ~ 35%, AUC<sub>0-∞</sub> by ~ 12%; all <i>p</i> &lt; 0.05). Adverse event incidence was 12.8% (fasting) and 25.0% (fed), with no serious adverse events reported.</p> Conclusion <p>The generic febuxostat formulation demonstrated PK equivalence to Feburic<sup>®</sup> under both fasting and fed conditions, with comparable safety profiles. The observed food effects, while statistically significant, support flexible administration without meal restrictions, meeting pharmacokinetic criteria for consideration as a therapeutic alternative in gout management.</p> Clinical trial registration <p>This study was prospectively registered (Registration No. CTR20233483; First Public Release Date: 1 November 2023) in the Chinese Clinical Trial Registration Platform (<a href="http://www.chinadrugtrials.org.cn">http://www.chinadrugtrials.org.cn</a>), a registry recognized by the Chinese National Medical Products Administration (NMPA). The trial was conducted from 28 November 2023 to 26 December 2023.</p>

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Bioequivalence evaluation of generic febuxostat versus Feburic® in healthy Chinese subjects: a randomized crossover study

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  • 发表日期：

    2025年10月6日

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  • Fengling Wang,
  • Xi Ye,
  • Fan Li,
  • Hulin Kong,
  • Minjie Liao,
  • Min Kan,
  • Juxiang Zhuang,
  • Angeng Wang,
  • Xiangyun Meng

摘要

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 (Cmax), area under the plasma concentration-time curve from time zero to the last time quantifiable time point (AUC0-t), and area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), 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: AUC0-t 99.08–104.28%, AUC0-∞ 98.73–103.84%, Cmax 92.87–112.14%; fed: AUC0-t 101.16–106.21%, AUC0-∞ 101.13–105.94%, Cmax 91.72–105.07%). High-fat meals delayed Tmax by 0.67 h and Tlag by 0.37 h (p < 0.05) while reducing systemic exposure (Cmax by ~ 35%, AUC0-∞ by ~ 12%; all p < 0.05). 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, meeting pharmacokinetic criteria for consideration as a therapeutic alternative in 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.