Probenecid decreases the efficacy of penicillin when used together initially, but this combination was historically exploited. The pharmacokinetic interaction responsible is:

• A Probenecid displaces penicillin from plasma albumin, increasing its volume of distribution and decreasing plasma levels
• B Probenecid competitively inhibits OAT1/OAT3 transporters in the renal proximal tubule, blocking penicillin secretion and increasing its plasma levels ✓
• C Probenecid induces CYP3A4, increasing penicillin metabolism and decreasing its levels
• D Probenecid competes with penicillin for renal glomerular filtration, reducing penicillin clearance

Explanation

Probenecid competitively inhibits organic anion transporter proteins (OAT1 and OAT3) on the basolateral membrane of renal proximal tubular cells, blocking the active tubular secretion of penicillins, cephalosporins, and other organic anions. By reducing renal elimination, probenecid raises and prolongs penicillin plasma levels — historically used during penicillin scarcity to extend antibiotic duration with lower doses. Note: the interaction increases, not decreases, penicillin efficacy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.