Cilastatin sodium

Cilastatin (MK-0791) is a potent, reversible, competitive inhibitor of renal dehydropeptidase I (DHP-I), exhibiting an IC₅₀ of 0.1 μM. By inhibiting DHP-I in the kidney, Cilastatin prevents the enzymatic degradation of β-lactam antibiotics, thereby enhancing their stability and therapeutic efficacy. In addition, Cilastatin demonstrates inhibitory activity against the bacterial metallo-β-lactamase enzyme CphA, with an IC₅₀ of 178 μM. Clinically and experimentally, Cilastatin is widely used as an antibacterial adjunct to improve antibiotic performance and reduce renal metabolism of co-administered β-lactam drugs.

Dipeptidase 1:0.3 ± 0.01 μM

Method: Purified porcine renal membrane dipeptidase was incubated with 0.1 mM imipenem and increasing concentrations of cilastatin, and imipenem hydrolysis was monitored spectrophotometrically at 299 nm.
Rresult: Cilastatin inhibited renal membrane dipeptidase-mediated imipenem hydrolysis with an IC50 of 0.3 ± 0.01 μM.[1]
Method: Porcine renal proximal tubular epithelial cells were treated with vancomycin at 0.6, 3, or 6 mg/mL with or without 200 μg/mL cilastatin for 24 h, and cell morphology and detachment were assessed.
Rresult: Cilastatin reduced vancomycin-induced morphological damage and significantly reduced cell detachment at 3 and 6 mg/mL vancomycin.[2]
Method: Vancomycin MIC and MBC values against eight clinical Staphylococcus aureus and Enterococcus isolates were determined in the presence or absence of 200 μg/mL cilastatin.
Rresult: Cilastatin did not compromise the inhibitory or bactericidal activity of vancomycin.[2]

Method: Kidney tubular injury was assessed histologically 48 h after blunt injury and treatment with intravenous cilastatin sodium or vehicle.
Rresult: Cilastatin reduced the tubular damage score by 45 ± 33% (p = 0.029).[3]

H2O: 80.00 mg/mL (210.28 mM), Sonication is recommended.