U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C16H26N2O5S
Molecular Weight 358.4547
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of CILASTATIN

SMILES

CC1(C)C[C@]1([H])C(=N/C(=C(/[H])\CCCCSC[C@@]([H])(C(=O)O)N)/C(=O)O)O

InChI

InChIKey=DHSUYTOATWAVLW-WFVMDLQDSA-N
InChI=1S/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1

HIDE SMILES / InChI

Molecular Formula C16H26N2O5S
Molecular Weight 358.4547
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB01597

PRIMAXIN® is a combination of cilastatin and imipenem. Cilastatin is a specific and reversible renal dehydropeptidase-I inhibitor. Imipenem is a penem antibacterial drug. 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. However, cilastatin in and of itself does not have any antibacterial activity. It also prevents the metabolism of leukotriene D4 to leukotriene E4 through the inhibition of leukotriene D4 dipeptidase.

CNS Activity

Curator's Comment:: Cerebrospinal fluid (CSF) penetration of imipenem-cilastatin was evaluated in 20 children (aged 4 months to 11 years) with central nervous system infections.

Originator

Curator's Comment:: # Merck & Co., Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.73 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
PRIMAXIN

Approved Use

Imipenem and Cilastatin for Injection, USP (I.V.) is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the conditions listed below: Lower respiratory tract infections. Staphylococcus aureus (penicillinase-producing strains), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzaeEfficacy for this organism in this organ system was studied in fewer than 10 infections. , Klebsiella species, Serratia marcescens Urinary tract infections (complicated and uncomplicated). Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii , Proteus vulgaris , Providencia rettgeri , Pseudomonas aeruginosa Intra-abdominal infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii , Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis, Fusobacterium species Gynecologic infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus agalactiae (Group B streptococci), Enterobacter species, Escherichia coli, Gardnerella vaginalis, Klebsiella species, Proteus species, Bifidobacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis Bacterial septicemia. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Enterobacter species, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species, Bacteroides species including B. fragilis Bone and joint infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Enterobacter species, Pseudomonas aeruginosa Skin and skin structure infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri , Pseudomonas aeruginosa, Serratia species, Peptococcus species, Peptostreptococcus species, Bacteroides species including B. fragilis, Fusobacterium species Endocarditis. Staphylococcus aureus (penicillinase-producing strains) Polymicrobic infections. Imipenem and Cilastatin for Injection, USP (I.V.) is indicated for polymicrobic infections including those in which S. pneumoniae (pneumonia, septicemia), S. pyogenes (skin and skin structure), or nonpenicillinase-producing S. aureus is one of the causative organisms. However, monobacterial infections due to these organisms are usually treated with narrower spectrum antibiotics, such as penicillin G. Imipenem and Cilastatin for Injection, USP (I.V.) is not indicated in patients with meningitis because safety and efficacy have not been established. For Pediatric Use information, see PRECAUTIONS, Pediatric Use, and DOSAGE AND ADMINISTRATION sections. Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria, Imipenem and Cilastatin for Injection, USP (I.V.) is useful for the treatment of mixed infections and as presumptive therapy prior to the identification of the causative organisms. Although clinical improvement has been observed in patients with cystic fibrosis, chronic pulmonary disease, and lower respiratory tract infections caused by Pseudomonas aeruginosa, bacterial eradication may not necessarily be achieved. As with other beta-lactam antibiotics, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Imipenem and Cilastatin for Injection, USP (I.V.). During therapy of Pseudomonas aeruginosa infections, periodic susceptibility testing should be done when clinically appropriate. Infections resistant to other antibiotics, for example, cephalosporins, penicillin, and aminoglycosides, have been shown to respond to treatment with Imipenem and Cilastatin for Injection, USP (I.V.). To reduce the development of drug-resistant bacteria and maintain the effectiveness of Imipenem and Cilastatin for Injection, USP (I.V.) and other antibacterial drugs, Imipenem and Cilastatin for Injection, USP (I.V.) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Launch Date

5.01811184E11
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
82.19 mg × h/L
500 mg 4 times / day multiple, intravenous
dose: 500 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: IMIPENEM
CILASTATIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.1 h
500 mg 4 times / day multiple, intravenous
dose: 500 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: IMIPENEM
CILASTATIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Other AEs: Diarrhoea, Hypertension...
Other AEs:
Diarrhoea (6%)
Hypertension (5%)
Constipation (4%)
Infusion site pain (3%)
Headache (5%)
Nausea (4%)
Cough (1%)
Vomiting (1%)
Hypokalaemia (3%)
Insomnia (2%)
Renal cyst (3%)
Infusion site erythema (2%)
Abdominal pain upper (3%)
Cardiac failure (2%)
Clostridium difficile colitis (3%)
Vaginal infection (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Cough 1%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Vomiting 1%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Cardiac failure 2%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Infusion site erythema 2%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Insomnia 2%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Vaginal infection 2%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Abdominal pain upper 3%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Clostridium difficile colitis 3%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Hypokalaemia 3%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Infusion site pain 3%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Renal cyst 3%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Constipation 4%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Nausea 4%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Headache 5%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Hypertension 5%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Diarrhoea 6%
1000 mg 3 times / day steady, intravenous
Recommended
Dose: 1000 mg, 3 times / day
Route: intravenous
Route: steady
Dose: 1000 mg, 3 times / day
Co-administed with::
IMIPENEM ANHYDROUS
Sources:
unhealthy, adult
n = 148
Health Status: unhealthy
Condition: infections
Age Group: adult
Sex: unknown
Population Size: 148
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 1470 uM]
yes [Ki 231 uM]
PubMed

PubMed

TitleDatePubMed
Inhibition of the mammalian beta-lactamase renal dipeptidase (dehydropeptidase-I) by (Z)-2-(acylamino)-3-substituted-propenoic acids.
1987 Jun
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Patents

Sample Use Guides

For adult patients with normal renal function (creatinine clearance of greater than or equal to 90 mL/min), the recommended PRIMAXIN® dosage regimens are: 500 mg every 6 hours OR 1000 mg every 8 hours OR 1000 mg every 6 hours.
Route of Administration: Intravenous
In Vitro Use Guide
Imipenem hydrolysis by both enzymes (human dehydropeptidase I and cphA from Aeromonas hydrophila) was seen to be cilastatin sensitive. The 50% inhibitory concentrations were 0.3 +/- 0.01 and 178 +/- 11 uM (n = 8), respectively.
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:18:06 UTC 2021
Edited
by admin
on Sat Jun 26 14:18:06 UTC 2021
Record UNII
141A6AMN38
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CILASTATIN
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
CILASTATIN [WHO-DD]
Common Name English
CILASTATIN [VANDF]
Common Name English
CILASTATIN [MI]
Common Name English
CILASTATIN [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
NDF-RT N0000175513
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
NDF-RT N0000175514
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.1 (IMI/CIL)
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
LIVERTOX 207
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
Code System Code Type Description
WIKIPEDIA
CILASTATIN
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
INN
5457
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
NCI_THESAURUS
C61679
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
CAS
82009-34-5
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL766
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
RXCUI
2540
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
640
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
MESH
D015377
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
EVMPD
SUB06264MIG
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
ECHA (EC/EINECS)
279-875-8
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
EPA CompTox
82009-34-5
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
FDA UNII
141A6AMN38
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
DRUG BANK
DB01597
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
IUPHAR
5166
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
LACTMED
Imipenem and Cilastatin
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
MERCK INDEX
M3544
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY Merck Index
PUBCHEM
6435415
Created by admin on Sat Jun 26 14:18:07 UTC 2021 , Edited by admin on Sat Jun 26 14:18:07 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY