Details of the Drug

General Information of Drug (ID: DM4S3O8)

• Drug Name: Ertapenem
• Synonyms: Ertapenem [INN]; Ertapenem (INN); Invanz (TN); (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; (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; (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

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 475.5
  Topological Polar Surface Area (xlogp); -1.5
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The clearance of drug is 1.8 L/h [3]
  Elimination: 38% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4 hours [4]
  Metabolism: The drug is metabolized via the hydrolysis of the beta-lactam ring [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 28.715 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.1% [4]
  Vd: The volume of distribution (Vd) of drug is 0.12 L/kg [3]
• Chemical Identifiers:
  Formula: C22H25N3O7S
  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
  Canonical SMILES: C[C@@H]1[C@@H]2[C@H](C(=O)N2C(=C1S[C@H]3C[C@H](NC3)C(=O)NC4=CC=CC(=C4)C(=O)O)C(=O)O)[C@@H](C)O
  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
  InChIKey: JUZNIMUFDBIJCM-ANEDZVCMSA-N
• Cross-matching ID:
  PubChem CID: 150610
  ChEBI ID: CHEBI:404903
  CAS Number: 153832-46-3
  DrugBank ID: DB00303
  TTD ID: D0Q1MS
  INTEDE ID: DR2457

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Beta-lactamase (blaB)	DEC3G7M	A0A1S7IV31_ENTAS	Substrate	[8]
Beta-lactamase (blaB)	DEMIUB2	BLAT_ECOLX	Substrate	[9]
Beta-lactamase (blaB)	DECWSA9	AMPC_MORMO	Substrate	[9]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ertapenem (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Mycophenolic acid	DMU65NK	Moderate	Altered absorption of Ertapenem due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[21]
Probenecid	DMMFWOJ	Minor	Decreased elimination of Ertapenem caused by Probenecid mediated competitive inhibition of renal tubular secretion.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[22]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Ertapenem and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[23]
Bupropion	DM5PCS7	Major	Increased risk of lowers seizure threshold by the combination of Ertapenem and Bupropion.	Nicotine use disorder [6C4A]	[24]
Lindane	DMB8CNL	Moderate	Increased risk of lowers seizure threshold by the combination of Ertapenem and Lindane.	Pediculosis [1G00]	[25]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Ertapenem due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[21]

References

• [1] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [2] BDDCS applied to over 900 drugs
• [3] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians
• [6] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [7] Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. JBacteriol. 2005 Mar;187(5):1815-24.
• [8] FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan. J Antimicrob Chemother. 2018 Nov 1;73(11):2969-2972.
• [9] War wound treatment complications due to transfer of an IncN plasmid harboring bla(OXA-181) from Morganella morganii to CTX-M-27-producing sequence type 131 Escherichia coli. Antimicrob Agents Chemother. 2015;59(6):3556-62.
• [10] Oral streptococcal strains isolated from odontogenic infections and their susceptibility to antibiotics. Rev Med Chir Soc Med Nat Iasi. 2006 Oct-Dec;110(4):1012-5.
• [11] Molecular investigation of extended-spectrum beta-lactamase genes and potential drug resistance in clinical isolates of Morganella morganii. Ann Saudi Med. 2016 May-Jun;36(3):223-8.
• [12] Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob Agents Chemother. 2002 May;46(5):1273-80.
• [13] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [15] Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus. Jpn J Antibiot. 1993 Jun;46(6):421-7.
• [16] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [17] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [18] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [19] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [20] Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23.
• [21] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [22] Product Information. Doribax (doripenem). Ortho McNeil Pharmaceutical, Raritan, NJ.
• [23] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [24] Product Information. Wellbutrin XL (buPROPion). GlaxoSmithKline, Philadelphia, PA.
• [25] Matsuoka LY "Convulsions following application of gamma benzene hexachloride." J Am Acad Dermatol 5 (1981): 98-9. [PMID: 6168673]