Cilastatin

Structural formula
General
Non-proprietary name	Cilastatin
other names	( Z ) -7 - [(2 R ) -2-amino-3-hydroxy-3-oxopropyl] sulfanyl-2 - {[(1 S ) -2,2-dimethylcyclopropanecarbonyl] amino} hept-2-enoic acid ( IUPAC ) ; Cilastatinum ( Latin INN ) ;
Molecular formula	C 16 H 26 N 2 O 5 S; C 16 H 25 N 2 NaO 5 S;
Brief description	white to light yellow, amorphous, hygroscopic powder (cilastatin sodium)
External identifiers / databases
EC number	279-875-8
ECHA InfoCard	100,072,592
PubChem	6435415
ChemSpider	4940183
DrugBank	DB01597
Wikidata	Q418201
Drug information
ATC code	J01 DH51 ( Imipenem -Cilastatin)
Drug class	Protease inhibitors
properties
Molar mass	358.45 g · mol -1 (cilastatin) ; 380.44 g · mol -1 (· cilastatin sodium) ;
solubility	very easily soluble in water and methanol , sparingly soluble in absolute ethanol , very sparingly soluble in dimethyl sulfoxide , practically insoluble in acetone and dichloromethane (cilastatin sodium)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Sodium salt	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	8000 mg kg −1 ( LD 50 , rat , oral , cilastatin) ; 6786 mg kg −1 ( LD 50 , mouse , iv , cilastatin sodium) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Cilastatin is an organic compound that is used as a medicinal substance . It competitively , reversibly and specifically inhibits the enzyme dehydropeptidase-I . Cilastatin is used in a fixed combination with imipenem (an antibiotic from the group of β-lactam antibiotics , subgroup: carbapenems ) in the treatment of infectious diseases. It prevents rapid metabolism ( metabolism ) of imipenem, so that antibacterially effective imipenem concentrations arise in plasma and urine. A reduction in the nephrotoxicity of imipenem was also observed in animal experiments . Cilastatin itself has no intrinsic antibacterial activity and does not affect the antibacterial effect of imipenem. Cilastatin was patented by Merck in 1979 and 1980 and is commercially available in combination with imipenem under the trade name Zienam by MSD Sharp & Dohme (MSD).

chemistry

Chemically, cilastatin is a derivative of the natural amino acid ( R ) - cysteine .

Trade names

Combination preparations

Commercial preparations contain cilastatin only in combination with imipenem : Tienam (CH), Zienam (A, D)

Individual evidence

↑ ^a ^b Data sheet CILASTATIN SODIUM CRS (PDF) at EDQM , accessed on July 18, 2009.
↑ ^a ^b data sheet cilastatin sodium salt from Sigma-Aldrich , accessed on March 23, 2011 ( PDF ).
↑ ^a ^b ^c Entry on cilastatin. In: Römpp Online . Georg Thieme Verlag, accessed on October 2, 2014.
↑ 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 . In: Antimicrobial Agents and Chemotherapy . 39, No. 7, July 1995, pp. 1629-1631. PMID 7492120 . PMC 162797 (free full text).

[Ph._Eur.-1] Data sheet CILASTATIN SODIUM CRS (PDF) at EDQM , accessed on July 18, 2009.

[Sigma-2] ta sheet cilastatin sodium salt from Sigma-Aldrich , accessed on March 23, 2011 ( PDF ).

[RÖMPP_Online-3] Entry on cilastatin. In: Römpp Online . Georg Thieme Verlag, accessed on October 2, 2014.

[pmid7492120-4] 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 . In: Antimicrobial Agents and Chemotherapy . 39, No. 7, July 1995, pp. 1629-1631. PMID 7492120 . PMC 162797 (free full text).