Other meanings of Cilastatin
Pharmacology
Cilastatin is a reversible inhibitor of renal dehydropeptidase I (DHP-I), an enzyme that inactivates the carbapenem antibiotic imipenem. It is co-administered with imipenem to prevent the antibiotic's rapid metabolism in the kidneys, thereby increasing its urinary concentration and therapeutic efficacy. Cilastatin itself has no antibacterial activity but is essential for the clinical use of imipenem, which is otherwise degraded within minutes. The combination is marketed under the brand name Primaxin (imipenem/cilastatin).
Cilastatin acts by reversibly inhibiting dehydropeptidase I, a zinc metalloenzyme located on the brush border of renal proximal tubular cells. This enzyme normally hydrolyzes the beta-lactam ring of imipenem, rendering it inactive. By blocking DHP-I, cilastatin protects imipenem from degradation, allowing it to reach therapeutic concentrations in the urinary tract. The inhibition is competitive and reversible, with cilastatin itself being excreted unchanged in the urine.1
Cilastatin is always administered intravenously in a fixed 1:1 ratio with imipenem, typically as imipenem/cilastatin (Primaxin). This combination is used to treat a wide range of infections, including intra-abdominal, respiratory, and urinary tract infections, as well as sepsis. By preserving imipenem's activity, cilastatin enhances its efficacy against Gram-positive, Gram-negative, and anaerobic bacteria. The combination is particularly valuable in hospital settings for empiric therapy of severe infections.
Cilastatin has a plasma half-life of approximately one hour and is primarily eliminated by the kidneys, with about 70% excreted unchanged. It does not cross the blood-brain barrier significantly, which is relevant because imipenem can cause neurotoxicity at high doses. Cilastatin is generally well tolerated; common adverse effects include nausea, diarrhea, and rash. It may also reduce the renal toxicity of imipenem by preventing the accumulation of toxic metabolites.2
Cilastatin has been investigated for potential nephroprotective effects beyond its role with imipenem. Studies suggest it may reduce acute kidney injury in animal models by inhibiting DHP-I in the kidney, which is involved in the metabolism of other compounds. Additionally, cilastatin has been shown to inhibit the enzyme in vitro, but its clinical significance outside of imipenem combination is limited. The development of cilastatin was a key step in making carbapenems clinically viable, as imipenem alone is rapidly degraded. The combination was approved by the FDA in 1985, and it remains a cornerstone in the treatment of multidrug-resistant infections.3
Cilastatin is always used in combination with imipenem; it is not available as a standalone drug.
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