Identification

Name
Imipenem
Accession Number
DB01598
Type
Small Molecule
Groups
Approved
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
  • Imipenem anhydrous
  • Imipenemum
  • N-formimidoyl thienamycin
  • N-formimidoylthienamycin
Product Ingredients
IngredientUNIICASInChI Key
Imipenem monohydrate71OTZ9ZE0A74431-23-5GSOSVVULSKVSLQ-JJVRHELESA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Imipenem and CilastatinImipenem monohydrate (500 mg/20mL) + Cilastatin sodium (500 mg/20mL)Injection, powder, for solutionIntravenousFresenius Kabi2012-01-03Not applicableUs
Imipenem and CilastatinImipenem monohydrate (250 mg/100mL) + Cilastatin sodium (250 mg/100mL)Injection, powder, for solutionIntravenousHospira, Inc.2011-11-16Not applicableUs
Imipenem and CilastatinImipenem monohydrate (250 mg/20mL) + Cilastatin sodium (250 mg/20mL)Injection, powder, for solutionIntravenousFresenius Kabi2012-01-03Not applicableUs
Imipenem and CilastatinImipenem monohydrate (500 mg/1) + Cilastatin sodium (500 mg/1)Injection, powder, for solutionIntravenousCardinal Health2012-01-032018-07-09Us
Imipenem and CilastatinImipenem monohydrate (500 mg/100mL) + Cilastatin sodium (500 mg/100mL)Injection, powder, for solutionIntravenousHospira, Inc.2011-11-16Not applicableUs
Imipenem and Cilastatin for InjectionImipenem (500 mg) + Cilastatin (500 mg)Powder, for solutionIntravenousPfizer2011-05-02Not applicableCanada
Imipenem and Cilastatin for InjectionImipenem (250 mg) + Cilastatin (250 mg)Powder, for solutionIntravenousPfizerNot applicableNot applicableCanada
Imipenem and Cilastatin for Injection USPImipenem (250 mg) + Cilastatin (250 mg)Powder, for solutionIntravenousSandoz Canada Incorporated2010-12-21Not applicableCanada
Imipenem and Cilastatin for Injection USPImipenem (500 mg) + Cilastatin (500 mg)Powder, for solutionIntravenousSandoz Canada Incorporated2010-12-21Not applicableCanada
Imipenem and Cilastatin for Injection, USPImipenem (500 mg) + Cilastatin (500 mg)Powder, for solutionIntravenousMylan PharmaceuticalsNot applicableNot applicableCanada
International/Other Brands
Tienamycin
Categories
UNII
Q20IM7HE75
CAS number
64221-86-9
Weight
Average: 299.346
Monoisotopic: 299.093976737
Chemical Formula
C12H17N3O4S
InChI Key
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

Pharmacology

Indication

For the treatment of bacterial infections caused by susceptible bacteria.

Associated Conditions
Pharmacodynamics

Imipenem 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 action

Imipenem 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.

TargetActionsOrganism
APenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 3
inhibitor
Bacillus subtilis (strain 168)
ABeta-lactamase
other/unknown
Staphylococcus aureus
Absorption

Imipenem is not effectively absorbed from the gastrointestinal tract and therefore must be administered parenterally.

Volume of distribution
Not Available
Protein binding

20% binds to plasma proteins

Metabolism

Renal.

Route of elimination
Not Available
Half life

1 hour

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Imipenem is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Imipenem is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Imipenem is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Imipenem is combined with Acenocoumarol.
AcepromazineImipenem may increase the neurotoxic activities of Acepromazine.
AceprometazineImipenem may increase the neurotoxic activities of Aceprometazine.
AcetophenazineAcetophenazine may increase the neurotoxic activities of Imipenem.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Imipenem.
AlimemazineAlimemazine may increase the neurotoxic activities of Imipenem.
AmineptineImipenem may increase the neurotoxic activities of Amineptine.
Food Interactions
Not 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
Human Metabolome Database
HMDB0015536
KEGG Compound
C06665
PubChem Compound
104838
PubChem Substance
46505744
ChemSpider
94631
BindingDB
50049708
ChEBI
471744
ChEMBL
CHEMBL148
Therapeutic Targets Database
DAP000459
PharmGKB
PA449968
Wikipedia
Imipenem
ATC Codes
J01DH51 — Imipenem and enzyme inhibitor

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentInfectious Diseases1
1RecruitingTreatmentAcinetobacter Baumannii Infection1
1, 2CompletedTreatmentPostmenopausal Endometrium1
1, 2TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2CompletedTreatmentAbdominal Abscess / Bacterial Infections / Pneumonia / Pneumonia, Bacterial / Ventilator-Associated Pneumonia (VAP)1
2CompletedTreatmentComplicated Urinary Tract Infections1
2CompletedTreatmentPyelonephritis / Urinary Tract Infections (UTIs)1
2CompletedTreatmentUrinary Tract Infections (UTIs)1
2TerminatedTreatmentPneumonia, Bacterial1
2TerminatedTreatmentUrinary Tract Infections (UTIs)1
3CompletedTreatmentAbscesses / Cellulitis / Skin-structure infections1
3CompletedTreatmentBacterial Infections1
3CompletedTreatmentComplicated Intra-Abdominal Infections / Complicated Urinary Tract Infections1
3CompletedTreatmentPneumonia, Bacterial1
3CompletedTreatmentHospital-acquired bacterial pneumonia1
3RecruitingTreatmentCritical Illness / Resistant Infection / Traumas1
3RecruitingTreatmentEnterobacteriaceae Infections1
3RecruitingTreatmentPneumonia, Bacterial1
4Active Not RecruitingTreatmentInfection NOS1
4CompletedNot AvailableVentilator-Associated Pneumonia (VAP)1
4CompletedPreventionAcute Pancreatitis (AP)1
4CompletedTreatmentInfective Endocarditis1
4CompletedTreatmentIntra-Abdominal Infections1
4CompletedTreatmentPatients With Febrile Neutropenia1
4CompletedTreatmentVentilator-Associated Pneumonia (VAP)1
4RecruitingTreatmentCritical Illness / Mechanical Ventilation Complication1
4RecruitingTreatmentSepsis1
4TerminatedTreatmentUrinary Tract Infections (UTIs)1
4Unknown StatusTreatmentLiver Cirrhosis1
4Unknown StatusTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA) / Ventilator-Associated Pneumonia (VAP)1
4Unknown StatusTreatmentVentilator-associated Bacterial Pneumonia1
Not AvailableCompletedTreatmentFebrile / Hematopoietic Stem Cell Transplantation (HSCT) / Neutropenias1
Not AvailableCompletedTreatmentSpontaneous Bacterial Peritonitis (SBP)1
Not AvailableCompletedTreatmentVentilator-associated Bacterial Pneumonia1
Not AvailableRecruitingNot AvailableChildren; Infection / Newborn; Infection1
Not AvailableRecruitingNot AvailableShock, Septic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Cardinal Health
  • Merck & Co.
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous
Powder, for solutionIntravenous
Injection, powder, for suspensionIntramuscular
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Thienamycins
Alternative Parents
Alpha amino acids and derivatives / Pyrroline carboxylic acids / Azepines / Vinylogous thioesters / Tertiary carboxylic acid amides / Thioenol ethers / Secondary alcohols / Azetidines / Sulfenyl compounds / Azacyclic compounds
show 10 more
Substituents
Thienamycin / Alpha-amino acid or derivatives / Pyrroline carboxylic acid / Pyrroline carboxylic acid or derivatives / Azepine / Vinylogous thioester / Pyrroline / Tertiary carboxylic acid amide / Azetidine / Carboxamide group
show 23 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
carbapenems (CHEBI:471744) / carbapenems (C06665)

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
Uniprot Name
Penicillin-binding protein 2
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 str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
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 str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
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
Uniprot Name
Penicillin-binding protein 3
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
Uniprot Name
Beta-lactamase
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]

Drug created on August 29, 2007 12:42 / Updated on November 02, 2018 09:10