Cilastatin

Renal injury is a common adverse reaction in antibacterial therapy. When carbapenem antibiotics such as imipenem are metabolized by renal dehydropeptidase-1 (DHP-1), nephrotoxic metabolites will be produced, which limits the clinical application of this class of broad-spectrum antibacterial agents. Cilastatin, as a specific inhibitor of DHP-1, has no significant antibacterial activity itself. It reversibly binds to DHP-1 on the surface of renal proximal tubule epithelial cells to block the intrarenal metabolism of imipenem, which not only reduces the risk of nephrotoxicity, but also increases the blood concentration and antibacterial activity of imipenem. At present, it is mainly formulated into a compound preparation with imipenem for the treatment of moderate to severe infections caused by susceptible bacteria, including lower respiratory tract infection, abdominal infection, sepsis, genitourinary system infection, etc. The applicable population includes adults and children over 3 months old, and it is a key component in the combined medication regimen for severe infections.

The market demand for cilastatin is highly bound to the clinical use scale of carbapenem compound preparations. In recent years, with the increase in the incidence of multidrug-resistant bacterial infections, the global market size of cilastatin-related preparations has exceeded 3 billion US dollars, with a compound annual growth rate maintained at around 4.2%. In terms of the domestic market, with the advancement of hierarchical diagnosis and treatment and the improvement of the construction of intensive care units, the in-hospital sales of imipenem and cilastatin preparations exceeded 7 billion yuan in 2023, of which generic drugs accounted for 68% of the market. The supply of active pharmaceutical ingredients (APIs) has formed a pattern dominated by domestic production, and the annual production capacity of leading enterprises can meet more than 90% of the domestic preparation production demand.

The original research enterprise of cilastatin is Merck & Co., Inc., and the compound preparation composed of cilastatin and imipenem is sold under the trade name Tienam®. Its core compound patent expired in the United States in 2009, and the relevant compound patent in China also expired in 2010. The main dosage form of the original marketed product is injection, with the conventional specification of 0.5g imipenem + 0.5g cilastatin. This product has been included in the *Catalogue of Reference Preparations for Chemical Drugs* of China, and is also listed as an FDA reference preparation. In terms of domestic API registration, more than 15 enterprises have obtained Class A status for their cilastatin APIs through registration with the Center for Drug Evaluation (CDE), which can be legally supplied for preparation production. Nearly 30 domestic enterprises have obtained marketing approval for imipenem and cilastatin for injection. (Data as of November 2024, please refer to the official website of CDE for the latest information)

CATO can provide a full set of impurity reference standards for cilastatin. Most of the products are in stock. For in-stock products, orders placed before 16:00 will be shipped on the same day. All products meet the compliance requirements of multiple regulatory systems such as the Chinese Pharmacopoeia and FDA, and can provide reliable reference material support for the quality research, stability study, impurity control and other links of API and preparation manufacturers.