QuickView for Cilastatin (compound)

Summary
General Info

PubChem

PubChem Compound 104867

Name:	Cilastatin
PubChem Compound ID:	104867
Description:	A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.
Molecular formula:	C₁₆H₂₆N₂O₅S
Molecular weight:	358.454 g/mol

DrugBank

Identification

Name:	Cilastatin
Name (isomeric):	DB01597
Drug Type:	small molecule
Description:	A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.
Brand name mixture:	Primaxin IV 500(Cilastatin Sodium + Imipenem), Primaxin 500(Cilastatin Sodium + Imipenem), Primaxin 250(Cilastatin Sodium + Imipenem)
Category:	Protease Inhibitors
CAS number:	82009-34-5

Pharmacology

Indication:	Combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect.
Pharmacology:	Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Dehydropeptidase is found in the kidney and is responsible for degrading 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 a... show more » Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Dehydropeptidase is found in the kidney and is responsible for degrading 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. show less «
Mechanism of Action:	Cilastatin is a specific and reversible renal dehydropeptidase-I inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to block the metabolism and thus the inactivation of imipenem so that antibacterial levels of imipenem can be... show more » Cilastatin is a specific and reversible renal dehydropeptidase-I inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to block the metabolism and thus the inactivation of imipenem so that antibacterial levels of imipenem can be attained in the urine. The drug also prevents the metabolism of leukotriene D4 to leukotriene E4 through the inhibition of leukotriene D4 dipeptidase. show less «
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Valganciclovir	Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)
Cyclosporine	Imipenem increases the effect and toxicity of cyclosporine

Targets

Dipeptidase 1

Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. Converts leukotriene D4 to leukotriene E4; it may play an important role in the regulation of leukotriene activity

UniProt ID:

P16444

Gene:

DPEP1

Actions:

inhibitor

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
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Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
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Farrell CA, Allegretto NJ, Hitchcock MJ: Cilastatin-sensitive dehydropeptidase I enzymes from three sources all catalyze carbapenem hydrolysis and conversion of leukotriene D4 to leukotriene E4. Arch Biochem Biophys. 1987 Jul;256(1):253-9.
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Kumon H, Nasu Y, Ohmori H, Kodama H, Konishi Y: [Effects of cilastatin sodium, an inhibitor of dehydropeptidase-I, on human urinary peptide excretion. Patients with renal insufficiency] Jpn J Antibiot. 1987 Sep;40(9):1571-83.
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Lin JH, Chen IW, Ulm EH: Dose-dependent kinetics of cilastatin in laboratory animals. Drug Metab Dispos. 1989 Jul-Aug;17(4):426-32.
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Richerson MA, Ambrose PG, Quintiliani R, Nightingale CH: Formulary review of the carbapenems: comparison of imipenem/cilastatin and meropenem. Conn Med. 1998 Mar;62(3):165-9.
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Hirota T, Nishikawa Y, Tanaka M, Igarashi T, Kitagawa H: Characterization of dehydropeptidase I in the rat lung. Eur J Biochem. 1986 Nov 3;160(3):521-5.
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Hirota T, Nishikawa Y, Komai T, Igarashi T, Kitagawa H: Role of dehydropeptidase-I in the metabolism of glutathione and its conjugates in the rat kidney. Res Commun Chem Pathol Pharmacol. 1987 May;56(2):235-42.
View Article

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
View Article

Keynan S, Hooper NM, Felici A, Amicosante G, Turner AJ: The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA. Antimicrob Agents Chemother. 1995 Jul;39(7):1629-31.
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Transporters

Solute carrier family 22 member 6

Solute carrier family 22 member 8

Solute carrier family 22 member 7