Imipenem is always combined with cilastatin in clinical formulations. The reason is that cilastatin:

• A Inhibits beta-lactamase enzymes in gram-negative bacteria, extending imipenem's spectrum
• B Enhances tubular secretion of imipenem, increasing urinary concentrations
• C Competes with imipenem for plasma protein binding, increasing free drug levels
• D Inhibits renal dehydropeptidase-I, preventing hydrolysis of imipenem in the proximal tubule ✓

Explanation

Imipenem is inactivated by dehydropeptidase-I (DHP-I) located on the brush border of renal proximal tubular cells, producing nephrotoxic metabolites and reducing urinary levels. Cilastatin is a specific DHP-I inhibitor that prevents this hydrolysis, restoring urinary drug levels and eliminating nephrotoxic metabolites. It has no beta-lactamase inhibitory activity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.