Indications
Cilastatin is utilized in combination with imipenem, with or without relebactam, to treat a variety of bacterial infections. These include infections of the respiratory tract, skin, bones, and gynecologic areas, as well as urinary tract infections, intra-abdominal infections, septicemia, and endocarditis.
Pharmacodynamics
Cilastatin functions as an inhibitor of the human enzyme dehydropeptidase. This enzyme is responsible for the degradation of the antibiotic imipenem. By inhibiting dehydropeptidase, cilastatin is administered intravenously alongside imipenem to prevent its breakdown and extend its antibacterial efficacy. It is important to note that cilastatin itself does not possess antibacterial properties. Additionally, the combination of cilastatin and imipenem can help avert proximal tubular necrosis, a potential side effect associated with high doses of imipenem.
Mechanism of Action
Cilastatin acts as a renal dehydropeptidase-I inhibitor, providing a crucial role in conjunction with the antibiotic imipenem. Dehydropeptidase-I, an enzyme located in the brush border of the renal tubules, is responsible for the hydrolysis of imipenem. To prevent this enzymatic degradation and ensure the therapeutic efficacy of imipenem, cilastatin is co-administered. By inhibiting dehydropeptidase-I, cilastatin effectively prevents the breakdown of imipenem, thereby enhancing its antibacterial activity.
