Cilastatin

Toxicity

In case of overdose with the combination product, including relebactam and imipenem, it is recommended to provide supportive care. Imipenem, cilastatin, and relebactam may be removed via hemodialysis.

Description

Cilastatin is an inhibitor of dipeptidase (dehydropeptidase I), a renal dipeptidase. It inhibits human renal dipeptidase (K_i = 0.7 μM), porcine dipeptidase (IC₅₀ = 0.11 μM), and bacterial metallo-β-lactamase CphA from A. hydrophila (IC₅₀ = 178 μM). Cilastatin (200 μg/ml) protects primary porcine renal proximal tubular epithelial cells from nephrotoxicity and apoptosis induced by vancomycin . In a mouse model of systemic infection, cilastatin in combination with imipenem protects mice from S. aureus, E. coli, and P. aeruginosa infection. Cilastatin was designed to inhibit renal metabolism of imipenem and prolong its half-life. Formulations containing cilastatin in combination with imipenem have been used to treat susceptible bacterial infections.

The Uses of Cilastatin

Cilastatin is used for treating diseases caused by polyresistant Gram-negative microorganisms and serious complex infections, including infection of S. aureus. Because of its strong activity against anaerobic bacteria, cilastatin is effective in monotherapy of intraabdominal infections. It is used for infectious diseases of the lower respiratory tract, urinary tract, gynecological infections, bacterial septicemia, and infections of the bones, skin, and so on.

Indications

Cilastatin is indicated, in combination with imipenem with or without relebactam, for the treatment of bacterial infections including respiratory, skin, bone, gynecologic, urinary tract, and intra-abdominal as well as septicemia and endocarditis.

What are the applications of Application

Cilastatin is a specific and reversible dehydropeptidase I inhibition

Background

Cilastatin is an inhibitor of renal dehydropeptidase, an enzyme responsible for both the metabolism of thienamycin beta-lactam antibiotics as well as conversion of leukotriene D4 to leukotriene E4. Since the antibiotic, imipenem, is one such antibiotic that is hydrolyzed by dehydropeptidase, cilastatin is used in combination with imipenem to prevent its metabolism. The first combination product containing both drugs was approved by the FDA in November of 1985 under the trade name Primaxin, marketed by Merck & Co. A newer triple-drug product was approved in July 2019 under the trade name Recarbrio which also contains relebactam.

Pharmacokinetics

Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Renal Dehydropeptidase degrades the antibiotic imipenem. Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. However, cilastatin in and of itself does not have any antibacterial activity. The increased renal excretion of unchanged imipenem appears to prevent proximal tubular necrosis associated with high doses of imipenem.

Metabolism

Not Available