Febuxostat is preferred over allopurinol for urate-lowering therapy in patients with moderate renal impairment. The key pharmacological difference is:
- A Febuxostat inhibits xanthine oxidase non-competitively and is primarily eliminated by hepatic metabolism with minimal renal excretion ✓
- B Allopurinol requires renal activation to its active metabolite oxypurinol which febuxostat does not
- C Febuxostat blocks both the oxidized and reduced forms of xanthine oxidase with higher potency
- D Febuxostat directly inhibits urate transporter URAT1 in the proximal tubule promoting uricosuria
Correct answer: A. Febuxostat inhibits xanthine oxidase non-competitively and is primarily eliminated by hepatic metabolism with minimal renal excretion
Explanation
Febuxostat is a non-purine selective inhibitor of xanthine oxidase that binds near but not at the molybdenum cofactor active site. Crucially, it is primarily metabolized by hepatic glucuronidation and oxidation via CYP1A2/2C8/2C9, with minimal renal excretion. In contrast, allopurinol's active metabolite oxypurinol is renally excreted and accumulates in renal impairment, increasing toxicity risk. Therefore, febuxostat can be used without dose adjustment at eGFR ≥30 mL/min.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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