A 55-year-old man with gout is prescribed febuxostat. How does febuxostat differ mechanistically from allopurinol in reducing uric acid production?

• A Febuxostat is a uricosuric agent increasing renal uric acid excretion, while allopurinol inhibits xanthine oxidase
• B Febuxostat inhibits PRPP synthetase reducing purine substrate, while allopurinol inhibits xanthine oxidase
• C Febuxostat promotes uric acid oxidation to allantoin, while allopurinol inhibits xanthine oxidase
• D Febuxostat is a non-purine, selective xanthine oxidase inhibitor that inhibits both oxidised and reduced forms of the enzyme, while allopurinol (a purine analogue) is converted to oxypurinol that inhibits only the reduced form ✓

Explanation

Febuxostat is a non-purine selective inhibitor of xanthine oxidase that inhibits both the oxidised (Mo[VI]) and reduced (Mo[IV]) forms of the enzyme through tight non-competitive binding. Allopurinol is a purine analogue that acts as a suicide substrate; it is converted by xanthine oxidase to oxypurinol (alloxanthine), which forms a stable inhibitory complex with the reduced (Mo[IV]) form of the enzyme only. Febuxostat is not metabolized to an active form and does not affect other purine metabolism enzymes, and has particular utility in patients with allopurinol hypersensitivity.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.