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Identification
NameImipenem
Accession NumberDB01598
TypeSmall Molecule
GroupsApproved
Description

Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [PubChem]

Structure
Thumb
Synonyms
(5R,6S)-3-((2-(Formimidoylamino)ethyl)thio)-6-((R)-1-hydroxyethyl)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid
(5R,6S)-3-(2-Formimidoylamino-ethylsulfanyl)-6-((R)-1-hydroxy-ethyl)-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid
(5R,6S)-6-((R)-1-Hydroxyethyl)-3-(2-(iminomethylamino)ethylthio)-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carbonsaeure
Imipemide
Imipenem
Imipenem anhydrous
Imipenem, n-formimidoyl thienamycin
Imipenemum
IMP
N-Formimidoyl thienamycin
N-formimidoylthienamycin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TienamycinNot Available
Brand mixtures
NameLabellerIngredients
Imipenem and CilastatinCardinal Health
Imipenem and Cilastatin for InjectionHospira Healthcare Corporation
Imipenem and Cilastatin for Injection USPSandoz Canada Incorporated
Imipenem and Cilastatin for Injection, USPMethapharm Inc
Primaxin 250Merck Canada Inc
Primaxin 500Merck Canada Inc
Primaxin IVMerck Sharp & Dohme Corp.
Primaxin IV 250/250 Add-vantage VialMerck Frosst Canada & Cie, Merck Frosst Canada & Co.
Primaxin IV 500Merck Canada Inc
Ran-imipenem-cilastatinRanbaxy Pharmaceuticals Canada Inc.
SaltsNot Available
Categories
UNII71OTZ9ZE0A
CAS number74431-23-5
WeightAverage: 299.346
Monoisotopic: 299.093976737
Chemical FormulaC12H17N3O4S
InChI KeyInChIKey=ZSKVGTPCRGIANV-ZXFLCMHBSA-N
InChI
InChI=1S/C12H17N3O4S/c1-6(16)9-7-4-8(20-3-2-14-5-13)10(12(18)19)15(7)11(9)17/h5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19)/t6-,7-,9-/m1/s1
IUPAC Name
(5R,6S)-3-({2-[(E)-(aminomethylidene)amino]ethyl}sulfanyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
SMILES
[H][C@]12CC(SCC\N=C\N)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thienamycins. These are beta-lactam antibiotics that differ from penicillins in having the thiazolidine sulfur atom replaced by carbon, the sulfur then becoming the first atom in the side chain.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentThienamycins
Alternative Parents
Substituents
  • Thienamycin
  • Alpha-amino acid or derivatives
  • Pyrroline carboxylic acid or derivatives
  • Pyrroline carboxylic acid
  • Azepine
  • Vinylogous thioester
  • Tertiary carboxylic acid amide
  • Pyrroline
  • Thioenolether
  • Tertiary amine
  • Secondary alcohol
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Sulfenyl compound
  • Carboximidamide
  • Thioether
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of bacterial infections caused by susceptible bacteria.
PharmacodynamicsImipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems. Imipenem has a broad spectrum of activity against aerobic and anaerobic Gram positive as well as Gram negative bacteria. It is particularly important for its activity against Pseudomonas aeruginosa and the Enterococcus species. Imipenem is rapidly degraded by the renal enzyme dehydropeptidase when administered alone, and is always co-administered with cilastatin to prevent this inactivation.
Mechanism of actionImipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria. This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to pencillin binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b. This preferential binding to PBP-2 and PBP-1b results in the direct conversion of the individual cell to a spheroblast, which leads to rapid cell lysis and death without filament formation.
Related Articles
AbsorptionImipenem is not effectively absorbed from the gastrointestinal tract and therefore must be administered parenterally.
Volume of distributionNot Available
Protein binding20% binds to plasma proteins
Metabolism

Renal.

Route of eliminationNot Available
Half life1 hour
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier-0.9711
Caco-2 permeable-0.6608
P-glycoprotein substrateSubstrate0.7111
P-glycoprotein inhibitor INon-inhibitor0.9011
P-glycoprotein inhibitor IINon-inhibitor0.8328
Renal organic cation transporterNon-inhibitor0.5947
CYP450 2C9 substrateNon-substrate0.7648
CYP450 2D6 substrateNon-substrate0.7854
CYP450 3A4 substrateNon-substrate0.5309
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9125
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9583
Ames testNon AMES toxic0.648
CarcinogenicityNon-carcinogens0.9203
BiodegradationNot ready biodegradable0.9309
Rat acute toxicity1.8089 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9852
hERG inhibition (predictor II)Non-inhibitor0.8603
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder for solutionintravenous
Injection, powder, for solutionintravenous
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility1E+004 mg/LMERCK INDEX (1996)
pKa3.2MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.776 mg/mLALOGPS
logP-0.19ALOGPS
logP-3.9ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.63ChemAxon
pKa (Strongest Basic)10.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area116.22 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity75.84 m3·mol-1ChemAxon
Polarizability31.1 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Maurizio Zenoni, “Imipenem production process.” U.S. Patent US20020095034, issued July 18, 2002.

US20020095034
General References
  1. Kattan JN, Villegas MV, Quinn JP: New developments in carbapenems. Clin Microbiol Infect. 2008 Dec;14(12):1102-11. doi: 10.1111/j.1469-0691.2008.02101.x. [PubMed:19076841 ]
  2. Pastel DA: Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination. Clin Pharm. 1986 Sep;5(9):719-36. [PubMed:3530614 ]
  3. Clissold SP, Todd PA, Campoli-Richards DM: Imipenem/cilastatin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1987 Mar;33(3):183-241. [PubMed:3552595 ]
  4. Buckley MM, Brogden RN, Barradell LB, Goa KL: Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1992 Sep;44(3):408-44. [PubMed:1382937 ]
  5. 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. [PubMed:9573653 ]
  6. Birnbaum J, Kahan FM, Kropp H, MacDonald JS: Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am J Med. 1985 Jun 7;78(6A):3-21. [PubMed:3859213 ]
  7. Hellinger WC, Brewer NS: Imipenem. Mayo Clin Proc. 1991 Oct;66(10):1074-81. [PubMed:1921491 ]
  8. Kahan FM, Kropp H, Sundelof JG, Birnbaum J: Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 Suppl D:1-35. [PubMed:6365872 ]
External Links
ATC CodesJ01DH51
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
CyclosporineCyclosporine may increase the neurotoxic activities of Imipenem.
GanciclovirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Imipenem.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Imipenem.
ProbenecidThe serum concentration of Imipenem can be increased when it is combined with Probenecid.
ValganciclovirThe risk or severity of adverse effects can be increased when Valganciclovir is combined with Imipenem.
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Imipenem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name:
mrdA
Uniprot ID:
P0AD65
Molecular Weight:
70856.1 Da
References
  1. Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. [PubMed:18076336 ]
  2. Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. [PubMed:17488146 ]
  3. Neu HC: Carbapenems: special properties contributing to their activity. Am J Med. 1985 Jun 7;78(6A):33-40. [PubMed:3873871 ]
  4. Luchi M, Morrison DC, Opal S, Yoneda K, Slotman G, Chambers H, Wiesenfeld H, Lemke J, Ryan JL, Horn D: A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with gram-negative urosepsis. Urosepsis Study Group. J Endotoxin Res. 2000;6(1):25-31. [PubMed:11061029 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
Gene Name:
mrcB
Uniprot ID:
P02919
Molecular Weight:
94291.875 Da
References
  1. Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. [PubMed:18076336 ]
  2. Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. [PubMed:17488146 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
Gene Name:
mrcA
Uniprot ID:
P02918
Molecular Weight:
93635.545 Da
References
  1. Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. [PubMed:18076336 ]
  2. Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. [PubMed:17488146 ]
Kind
Protein
Organism
Bacillus subtilis (strain 168)
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
pbpC
Uniprot ID:
P42971
Molecular Weight:
74405.915 Da
References
  1. Nicolau DP: Carbapenems: a potent class of antibiotics. Expert Opin Pharmacother. 2008 Jan;9(1):23-37. [PubMed:18076336 ]
  2. Zhanel GG, Wiebe R, Dilay L, Thomson K, Rubinstein E, Hoban DJ, Noreddin AM, Karlowsky JA: Comparative review of the carbapenems. Drugs. 2007;67(7):1027-52. [PubMed:17488146 ]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
yes
Actions
other/unknown
General Function:
Beta-lactamase activity
Specific Function:
Not Available
Gene Name:
blaZ
Uniprot ID:
P00807
Molecular Weight:
31348.98 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Pichardo C, Rodriguez-Martinez JM, Pachon-Ibanez ME, Conejo C, Ibanez-Martinez J, Martinez-Martinez L, Pachon J, Pascual A: Efficacy of cefepime and imipenem in experimental murine pneumonia caused by porin-deficient Klebsiella pneumoniae producing CMY-2 beta-Lactamase. Antimicrob Agents Chemother. 2005 Aug;49(8):3311-6. [PubMed:16048941 ]
  3. Jeon BC, Jeong SH, Bae IK, Kwon SB, Lee K, Young D, Lee JH, Song JS, Lee SH: Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in korea. J Clin Microbiol. 2005 May;43(5):2241-5. [PubMed:15872249 ]
  4. Fenollar-Ferrer C, Donoso J, Frau J, Munoz F: Molecular modeling of Henry-Michaelis and acyl-enzyme complexes between imipenem and Enterobacter cloacae P99 beta-lactamase. Chem Biodivers. 2005 May;2(5):645-56. [PubMed:17192008 ]
  5. Neu HC: Carbapenems: special properties contributing to their activity. Am J Med. 1985 Jun 7;78(6A):33-40. [PubMed:3873871 ]
  6. Kahan FM, Kropp H, Sundelof JG, Birnbaum J: Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 Suppl D:1-35. [PubMed:6365872 ]
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Drug created on August 29, 2007 12:42 / Updated on September 16, 2013 17:15