A 45-year-old patient with gout and renal impairment (CrCl 40 mL/min) is being considered for urate-lowering therapy. Probenecid is contraindicated in this patient primarily because:

• A Probenecid is nephrotoxic at the doses required for urate lowering in renal impairment
• B Probenecid inhibits CYP2C9, causing dangerous accumulation of co-administered urate-lowering drugs
• C Probenecid increases uricosuria, causing hyperuricosuria and renal stone formation even at normal GFR
• D Probenecid acts by blocking renal tubular reabsorption of urate, a mechanism that requires adequate renal tubular function and GFR above 50-60 mL/min to be effective ✓

Explanation

Probenecid lowers serum uric acid by blocking URAT1-mediated reabsorption of uric acid in the proximal renal tubule, thereby increasing urinary uric acid excretion. This mechanism requires sufficient nephron mass and GFR (generally >50 mL/min) to be effective; in moderate to severe renal impairment, there are fewer functioning tubules, the drug is poorly effective, and the risk of uric acid crystalluria in the already-impaired kidney increases. Allopurinol or febuxostat (xanthine oxidase inhibitors) are preferred in renal impairment. Probenecid inhibits OAT transporters, not CYP2C9 primarily.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.