Details of the Drug

General Information of Drug (ID: DMI9FBP)

Drug Name
Imipenem
Synonyms
Imipemide; Tienamycin; Imipenem anhydrous; Imipenem (INN); N-Formimidoylthienamycin; Primaxin (TN); Imipenem, N-Formimidoyl thienamycin; [5R-[5.alpha.,6.alpha.(R*)]]-6-(1-Hydroxyethyl)-3-[[2-[(iminomethyl)amino]ethyl]thio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate; (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)-3-[2-(aminomethylideneamino)ethylsulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[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; (5R,6S)-6-[(1R)-1-hydroxyethyl]-3-({2-[(iminomethyl)amino]ethyl}thio)-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
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 299.35
Topological Polar Surface Area (xlogp) -0.7
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
Clearance
The renal clearance of drug is 0.05 L/h/kg [3]
Elimination
69% 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 1 hour [4]
Metabolism
The drug is metabolized via renal dehydropeptidase [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 222.819 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.86% [4]
Vd
The volume of distribution (Vd) of drug is 0.23-0.31 L/kg [7]
Water Solubility
The ability of drug to dissolve in water is measured as 10 mg/mL [2]
Chemical Identifiers
Formula
C12H17N3O4S
IUPAC Name
(5R,6S)-3-[2-(aminomethylideneamino)ethylsulfanyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
Canonical SMILES
C[C@H]([C@@H]1[C@H]2CC(=C(N2C1=O)C(=O)O)SCCN=CN)O
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
InChIKey
ZSKVGTPCRGIANV-ZXFLCMHBSA-N
Cross-matching ID
PubChem CID
104838
ChEBI ID
CHEBI:471744
CAS Number
64221-86-9
DrugBank ID
DB01598
TTD ID
D0H3TD
INTEDE ID
DR2447

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial Penicillin binding protein 2 (Bact mrdA) TTHWB7G MRDA_ECOLI Binder [8], [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Beta-lactamase (blaB) DE7IH52 AMPC_CITFR Substrate [10]
Beta-lactamase (blaB) DEC3G7M A0A1S7IV31_ENTAS Substrate [11], [12]
Beta-lactamase (blaB) DEYIEO5 AMPC_SERMA Substrate [10], [13]
Carbapenemase (cphA) DEB90AL BLAB_AERHY Substrate [14], [15]
Beta-lactamase (blaB) DEBKS91 A0A1B1FBM9_ACIBA Substrate [16]
AmpC beta-lactamase (ampC) DERI7LO A0A0H3KQ39_BURM1 Substrate [17]
Carbapenemase (cphA) DETRKSD A0A3G1JAD7_ALCXX Substrate [18]
Beta-lactamase (blaB) DECWSA9 AMPC_MORMO Substrate [19]
Beta-lactamase (blaB) DEUHIQS A0A1S7IV31_ENTAS Substrate [20], [21]
Beta-lactamase (blaB) DECB2MX A0A1M5PLB6_9FLAO Substrate [22]
Beta-lactamase (blaB) DEEQ3RW K0GG60_CITBR Substrate [23]
Beta-lactamase (blaB) DEQ0K5J A0A223JZR3_9ENTR Substrate [23]
Beta-lactamase (blaB) DE7MYGB A0A291NY45_PROSP Substrate [10]
Beta-lactamase (blaB) DEL6894 A0A2S8DM15_SHIBO Substrate [23]
Beta-lactamase (blaB) DE8KH4C A0A3B7D7C4_9VIBR Substrate [24]
Carbapenemase (cphA) DEQ4LIN Q8L1M8_9ENTR Substrate [25]
Carbapenemase (cphA) DE9QNXV A0A366EJX1_9ENTR Substrate [26]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Imipenem (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Polyethylene glycol DM4I1JP Moderate Increased risk of lowers seizure threshold by the combination of Imipenem and Polyethylene glycol. Irritable bowel syndrome [DD91] [38]
Valganciclovir DMS2IUH Moderate Increased risk of lowers seizure threshold by the combination of Imipenem and Valganciclovir. Virus infection [1A24-1D9Z] [39]

References

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2 BDDCS applied to over 900 drugs
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4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
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 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.
8 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.
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10 Antibiotic therapy for inducible AmpC beta-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides? Int J Antimicrob Agents. 2012 Oct;40(4):297-305.
11 FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan. J Antimicrob Chemother. 2018 Nov 1;73(11):2969-2972.
12 Survey of clinical extended-spectrum beta-lactamase-producing Enterobacter cloacae isolates in a Chinese Tertiary Hospital, 2012-2014. Microb Drug Resist. 2017 Jan;23(1):83-89.
13 Serratia marcescens producing SME carbapenemases: an emerging resistance problem in the UK? J Antimicrob Chemother. 2017 May 1;72(5):1535-1537.
14 A carbapenem-resistant clinical isolate of Aeromonas hydrophila in Japan harbouring an acquired gene encoding GES-24 beta-lactamase. J Med Microbiol. 2018 Nov;67(11):1535-1537.
15 Chronic colitis after Aeromonas infection. Gut. 1989 May;30(5):686-90. Case Reports
16 A high mortality rate associated with multidrug-resistant Acinetobacter baumannii ST79 and ST25 carrying OXA-23 in a Brazilian intensive care unit. PLoS One. 2018 Dec 28;13(12):e0209367.
17 Characterization of the AmpC beta-Lactamase from Burkholderia multivorans. Antimicrob Agents Chemother. 2018 Sep 24;62(10). pii: e01140-18.
18 Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans. Sci Rep. 2018 May 25;8(1):8181.
19 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.
20 AmpC beta-lactamase-producing Enterobacterales: what a clinician should know. Infection. 2019 Jun;47(3):363-375.
21 Molecular analysis of colonized bacteria in a human newborn infant gut. J Microbiol. 2005 Aug;43(4):345-53.
22 Whole-genome sequence of Chryseobacterium oranimense, a colistin-resistant bacterium isolated from a cystic fibrosis patient in France. Antimicrob Agents Chemother. 2015 Mar;59(3):1696-706.
23 Hospital sewage water: a reservoir for variants of New Delhi metallo-beta-lactamase (NDM)- and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Int J Antimicrob Agents. 2018 Jan;51(1):82-88.
24 Carbapenemase VCC-1-producing Vibrio cholerae in coastal waters of Germany. Emerg Infect Dis. 2017 Oct;23(10):1735-1737.
25 Occurrence of a new metallo-beta-lactamase IMP-4 carried on a conjugative plasmid in Citrobacter youngae from the People's Republic of China. FEMS Microbiol Lett. 2001 Jan 1;194(1):53-7.
26 Pseudocitrobacter gen. nov., a novel genus of the Enterobacteriaceae with two new species Pseudocitrobacter faecalis sp. nov., and Pseudocitrobacter anthropi sp. nov, isolated from fecal samples from hospitalized patients in Pakistan. Syst Appl Microbiol. 2014 Feb;37(1):17-22.
27 Detection and characterization of beta-lactamase genes in subgingival bacteria from patients with refractory periodontitis. FEMS Microbiol Lett. 2005 Jan 15;242(2):319-24.
28 Citrobacter freundii bacteremia: Risk factors of mortality and prevalence of resistance genes. J Microbiol Immunol Infect. 2018 Aug;51(4):565-572.
29 Analyses of a ceftazidime-avibactam-resistant Citrobacter freundii isolate carrying blaKPC-2 reveals a heterogenous population and reversible genotype. mSphere. 2018 Sep 26;3(5). pii: e00408-18.
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31 Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens. Niger J Clin Pract. 2019 Jan;22(1):125-130.
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