Imipenem is always combined with cilastatin in clinical formulations. The purpose of cilastatin is:
- A Inhibition of renal brush border dehydropeptidase-I to prevent inactivation of imipenem ✓
- B Synergistic antibacterial activity against Pseudomonas
- C Prevention of seizure-inducing metabolites by inhibiting CNS metabolism
- D Enhancing oral bioavailability of imipenem by blocking intestinal esterases
Correct answer: A. Inhibition of renal brush border dehydropeptidase-I to prevent inactivation of imipenem
Explanation
Imipenem is metabolized in the renal proximal tubular brush border by the enzyme dehydropeptidase-I (DHP-I), which converts it to a nephrotoxic metabolite and reduces urinary drug concentration. Cilastatin is a specific DHP-I inhibitor; it has no antibacterial activity itself but protects imipenem from renal metabolism, raising drug concentration in urine and eliminating nephrotoxicity. This is why the combination is 1:1 (imipenem:cilastatin 500 mg:500 mg). Meropenem does not require cilastatin because it is intrinsically resistant to DHP-I.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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