Probenecid lowers serum urate by increasing urinary uric acid excretion. Its molecular target and an important limitation are:

• A Inhibits xanthine oxidase; ineffective in tumour lysis syndrome
• B Blocks tubular secretion of urate; increases risk of uric acid stones
• C Converts urate to allantoin; contraindicated with penicillins
• D Inhibits URAT1 transporter in proximal tubule; ineffective when creatinine clearance falls below about 30 mL/min ✓

Explanation

Probenecid blocks the URAT1 (urate-anion exchanger) in the proximal tubular brush border, preventing urate reabsorption and promoting its excretion. Because it acts on active tubular transport, it loses efficacy once creatinine clearance drops below roughly 30 mL/min, making it unsuitable in advanced renal failure. It also blocks tubular secretion of penicillin, which was historically exploited to prolong penicillin levels, so option C states the opposite of its drug interaction. Xanthine oxidase inhibition defines allopurinol and febuxostat.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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