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Identification
NameErtapenem
Accession NumberDB00303  (APRD00952)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Ertapenem is a carbapenem antibiotic marketed by Merck as Invanz®. It is structurally very similar to meropenem in that it possess a 1-beta-methyl group. [Wikipedia]

Structure
Thumb
Synonyms
(1R,5S,6S,8R,2'S,4's)-2-(2-(3-carboxyphenylcarbamoyl)pyrrolidin-4-ylthio)-6-(1-hydroxyethyl)-1-methylcarbapenem-3-carboxylic acid
(4R,5S,6S)-3-((3S,5S)-5-((3-Carboxyphenyl)carbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid
ERTAPENEM
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Invanzinjection, powder, lyophilized, for solution1 g/1intramuscular; intravenousMerck Sharp & Dohme Corp.2001-11-21Not applicableUs
Invanzpowder for solution1 gintramuscular; intravenousMerck Canada Inc2003-08-27Not applicableCanada
Invanzinjection, powder, lyophilized, for solution1 g/1intravenousMerck Sharp & Dohme Corp.2001-11-21Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ertapenem sodium
ThumbNot applicableDBSALT001460
Categories
UNIIG32F6EID2H
CAS number153832-46-3
WeightAverage: 475.515
Monoisotopic: 475.141320859
Chemical FormulaC22H25N3O7S
InChI KeyInChIKey=JUZNIMUFDBIJCM-ANEDZVCMSA-N
InChI
InChI=1S/C22H25N3O7S/c1-9-16-15(10(2)26)20(28)25(16)17(22(31)32)18(9)33-13-7-14(23-8-13)19(27)24-12-5-3-4-11(6-12)21(29)30/h3-6,9-10,13-16,23,26H,7-8H2,1-2H3,(H,24,27)(H,29,30)(H,31,32)/t9-,10-,13+,14+,15-,16-/m1/s1
IUPAC Name
(4R,5S,6S)-3-{[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
SMILES
[H][C@]12[C@@H](C)C(S[C@]3([H])CN[C@@]([H])(C3)C(=O)NC3=CC=CC(=C3)C(O)=O)=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 amide
  • N-arylamide
  • Aminobenzoic acid or derivatives
  • Aminobenzoic acid
  • Alpha-amino acid or derivatives
  • Benzoic acid
  • Benzoic acid or derivatives
  • Pyrroline carboxylic acid or derivatives
  • Pyrroline carboxylic acid
  • Pyrrolidine-2-carboxamide
  • Pyrrolidine carboxylic acid or derivatives
  • Benzoyl
  • Azepine
  • Vinylogous thioester
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Tertiary carboxylic acid amide
  • Pyrroline
  • Pyrrolidine
  • Thioenolether
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Sulfenyl compound
  • Thioether
  • Secondary amine
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment the following moderate to severe infections caused by susceptible isolates of the designated microorganisms: (1) complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis, (2) complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia, (3) community acquired pneumonia due to Streptococcus pneumoniae (penicillin susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis, (4) complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae, (5) acute pelvic infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species, or Prevotella bivia.
PharmacodynamicsErtapenem has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria.
Mechanism of actionThe bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Ertapenem is hydrolyzed by metallo-beta-lactamases.
Related Articles
AbsorptionErtapenem is almost completely absorbed following intramuscular administration. The bioavailability of a 1 g intramuscular dose approximated 92% in 26 healthy subjects [77% male; median (range) age, 29 (22–41) years]. Plasma concentrations of total ertapenem were similar whether given intramuscularly or intravenously.
Volume of distribution
  • 0.12 liter/kg [adults]
  • 0.2 liter/kg [pediatric, 3 months to 12 years]
  • 0.16 liter/kg [pediatric patients 13 to 17 years]
Protein bindingErtapenem is highly bound to human plasma proteins, primarily albumin, in a concentration-dependent manner. The protein binding of ertapenem decreases as plasma concentrations increase. At a plasma concentration of <100 µg/mL, approximately 95% of ertapenem is protein bound. Protein binding of ertapenem decreases to approximately 85% at an approximate plasma concentration of 300 µg/mL.
Metabolism

The major metabolite is the inactive ring-opened derivative formed by hydrolysis of the β-lactam ring. Ertapenem did not inhibit metabolism mediated by cytochrome P450 (CYP) isoforms 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4 when evaluated by in vitro studies in human liver microsomes. Ertapenem is neither a substrate nor an inhibitor of P-glycoprotein or cytochrome P450 enzymes; significant drug interactions between ertapenem and drugs handled by these systems are not expected [PMID: 15150180]

Route of eliminationOf the 80% recovered in urine, approximately 38% is excreted as unchanged drug and approximately 37% as the ring-opened metabolite.
Half lifeThe mean plasma half-life is approximately 4 hours.
Clearance
  • 1.8 L/h
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+0.5982
Blood Brain Barrier-0.9811
Caco-2 permeable-0.7052
P-glycoprotein substrateSubstrate0.7716
P-glycoprotein inhibitor INon-inhibitor0.917
P-glycoprotein inhibitor IINon-inhibitor0.9955
Renal organic cation transporterNon-inhibitor0.9253
CYP450 2C9 substrateNon-substrate0.7891
CYP450 2D6 substrateNon-substrate0.8229
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.8677
CYP450 2C9 inhibitorNon-inhibitor0.867
CYP450 2D6 inhibitorNon-inhibitor0.8964
CYP450 2C19 inhibitorNon-inhibitor0.8511
CYP450 3A4 inhibitorNon-inhibitor0.9658
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9695
Ames testNon AMES toxic0.6766
CarcinogenicityNon-carcinogens0.8052
BiodegradationNot ready biodegradable0.9821
Rat acute toxicity2.0803 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9947
hERG inhibition (predictor II)Non-inhibitor0.8848
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintramuscular; intravenous1 g/1
Injection, powder, lyophilized, for solutionintravenous1 g/1
Powder for solutionintramuscular; intravenous1 g
Prices
Unit descriptionCostUnit
Invanz 1 gm add-vantage vial72.85USD vial
Invanz 1 gm vial69.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2106370 No2003-11-252013-02-02Canada
US5478820 Yes1996-05-212016-05-21Us
US5652233 No1993-02-022013-02-02Us
US5952323 Yes1997-11-152017-11-15Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySoluble as sodium saltNot Available
logP0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.286 mg/mLALOGPS
logP-0.2ALOGPS
logP-3.2ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.37ChemAxon
pKa (Strongest Basic)9.03ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area156.27 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity121.8 m3·mol-1ChemAxon
Polarizability48.77 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Ying Shi, Kun Li, Zan Xie, Xuebin Zhao, Jian Lv, Xiuqin Yu, “INTERMEDIATE OF ERTAPENEM, A COMPOSITION COMPRISING THE SAME AND PREPARATION METHODS THEREOF.” U.S. Patent US20120095209, issued April 19, 2012.

US20120095209
General References
  1. Nix DE, Majumdar AK, DiNubile MJ: Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians. J Antimicrob Chemother. 2004 Jun;53 Suppl 2:ii23-8. [PubMed:15150180 ]
External Links
ATC CodesJ01DH03
AHFS Codes
  • 08:12.07.08
PDB EntriesNot Available
FDA labelDownload (140 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Ertapenem.
ProbenecidThe serum concentration of Ertapenem can be increased when it is combined with Probenecid.
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Ertapenem.
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Ertapenem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. Its synthesize cross-linked peptidoglycan from the lipid intermediates (By similarity).
Gene Name:
mrdA
Uniprot ID:
P44469
Molecular Weight:
73812.47 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. 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. [PubMed:17016423 ]
  3. Odenholt I: Ertapenem: a new carbapenem. Expert Opin Investig Drugs. 2001 Jun;10(6):1157-66. [PubMed:11772242 ]
  4. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
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. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Peptidoglycan glycosyltransferase activity
Specific Function:
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum. Catalyzes the synthesis of cross-linked peptidoglycan from the lipid-linked precursors.
Gene Name:
ftsI
Uniprot ID:
P45059
Molecular Weight:
67165.845 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. 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. [PubMed:17016423 ]
  3. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Peptidoglycan glycosyltransferase activity
Specific Function:
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan from the lipid-linked precursors (PubMed:7030331). Required for localization of FtsN (PubMed:9282742).
Gene Name:
ftsI
Uniprot ID:
P0AD68
Molecular Weight:
63876.925 Da
References
  1. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction.
Gene Name:
dacB
Uniprot ID:
P24228
Molecular Weight:
51797.85 Da
References
  1. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
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. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
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. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Gene Name:
dacC
Uniprot ID:
P08506
Molecular Weight:
43608.595 Da
References
  1. Kohler J, Dorso KL, Young K, Hammond GG, Rosen H, Kropp H, Silver LL: In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum beta-lactamase-and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother. 1999 May;43(5):1170-6. [PubMed:10223931 ]
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Drug created on June 13, 2005 07:24 / Updated on August 24, 2016 03:05