Febuxostat is preferred over allopurinol in patients with severe renal impairment for gout. What is the mechanism of febuxostat's xanthine oxidase inhibition?

• A Febuxostat is a purine analogue that competes with xanthine at the active site
• B Febuxostat undergoes oxidation by xanthine oxidase to form an irreversible suicide inhibitor
• C Febuxostat is a prodrug converted by aldehyde oxidase to the active inhibitor
• D Febuxostat is a non-purine selective inhibitor that binds a channel leading to the molybdopterin active site, blocking both oxidised and reduced forms of xanthine oxidase ✓

Explanation

Febuxostat is a non-purine selective inhibitor of xanthine oxidase; it binds within a narrow channel leading to the molybdopterin centre and inhibits both the oxidised (Mo-VI) and reduced (Mo-IV) forms of the enzyme, unlike allopurinol which only inhibits the reduced form. Allopurinol is a purine analogue (hypoxanthine analogue) that is also metabolised by xanthine oxidase. Febuxostat is predominantly hepatically metabolised and can be used without dose adjustment in mild-moderate renal impairment.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.