How does probenecid affect penicillin metabolism?

How does probenecid affect penicillin metabolism?

• A. Increases renal clearance causing decreased plasma levels
• B. Increases plasma levels without affecting clearance
• C. Decreases renal clearance causing increased plasma levels
• D. No effect on penicillin metabolism

Answer: (C)

The key idea is that penicillin is cleared by the kidneys largely through active tubular secretion. Probenecid blocks the organic acid transporters in the proximal tubule that mediate this secretion, so renal clearance of penicillin decreases. With less being excreted per unit time, plasma levels rise and the drug stays in the bloodstream longer. This interaction is about excretion, not metabolic breakdown, so penicillin metabolism isn’t increased. Thus the effect is decreased renal clearance leading to increased plasma levels.

The key idea is that penicillin is cleared by the kidneys largely through active tubular secretion. Probenecid blocks the organic acid transporters in the proximal tubule that mediate this secretion, so renal clearance of penicillin decreases. With less being excreted per unit time, plasma levels rise and the drug stays in the bloodstream longer. This interaction is about excretion, not metabolic breakdown, so penicillin metabolism isn’t increased. Thus the effect is decreased renal clearance leading to increased plasma levels.