Details of the Drug

General Information of Drug (ID: DM62UHC)

Drug Name
Meropenem
Synonyms
MEPM; MERONEM; Meropen; Merrem; Meropenem anhydrous; Mepem (TN); Meronem (TN); Meropen (TN); Meropenem (INN); Merrem (TN); Neopenem (TN); SM-7338; Meronem; Merrem I.V. (TN); (1R,5S,6S)-2-[(3S,5S)-5-(dimethylaminocarbonyl)pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid trihydrate; (2S,3R,4R)-2-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-{[(3S,5R)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-3-methyl-3,4-dihydro-2H-pyrrole-5-carboxylic acid; (4R,5S,6S)-3-[(3S,5S)-5-(dimethylcarbamoyl)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-(dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; (5S,6S)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((S)-1-hydroxyethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid; (6S)-2-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-6-[(1R)-1-hydroxyethyl]-1beta-methyl-2,3-didehydro-1-carbapenam-3-carboxylic acid
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [1]
Meningococcal meningitis N.A. Approved [2]
Peritonitis N.A. Approved [2]
Pneumococcal meningitis N.A. Approved [2]
Pseudomonas aeruginosa infectious disease N.A. Approved [2]
Therapeutic Class
Antibiotics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 383.5
Logarithm of the Partition Coefficient (xlogp) -2.4
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 3.9 mL/min/kg [4]
Elimination
70% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 1 hour [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 111.761 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.87% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.3 L/kg [4]
Chemical Identifiers
Formula
C17H25N3O5S
IUPAC Name
(4R,5S,6S)-3-[(3S,5S)-5-(dimethylcarbamoyl)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)N(C)C)C(=O)O)[C@@H](C)O
InChI
InChI=1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1
InChIKey
DMJNNHOOLUXYBV-PQTSNVLCSA-N
Cross-matching ID
PubChem CID
441130
ChEBI ID
CHEBI:43968
CAS Number
96036-03-2
DrugBank ID
DB00760
TTD ID
D0O5FY
VARIDT ID
DR01200
INTEDE ID
DR2491
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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 Modulator [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
New delhi metallo-beta-lactamase NDM-1 (blaNDM) DEBGCYQ A0A345N7K5_SALET Substrate [8]
Beta-lactamase (blaB) DEC3G7M A0A1S7IV31_ENTAS Substrate [9]
Beta-lactamase (blaB) DENJ2SQ BLAB_BACFG Substrate [10]
Carbapenemase (cphA) DEB90AL BLAB_AERHY Substrate [11], [12]
Beta-lactamase (blaB) DEBKS91 A0A1B1FBM9_ACIBA Substrate [13]
Beta-lactamase (blaB) DECWSA9 AMPC_MORMO Substrate [14]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
HLA class I histocompatibility antigen, alpha chain G (HLA-G) OTMLK1KN HLAG_HUMAN Gene/Protein Processing [15]
HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) OTKADDUB DOB_HUMAN Gene/Protein Processing [15]
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 Meropenem (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Mycophenolic acid DMRBMAU Moderate Altered absorption of Meropenem due to GI flora changes caused by Mycophenolic acid. Crohn disease [DD70] [16]
Probenecid DMMFWOJ Moderate Decreased elimination of Meropenem caused by Probenecid mediated competitive inhibition of renal tubular secretion. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [17]
Polyethylene glycol DM4I1JP Moderate Increased risk of lowers seizure threshold by the combination of Meropenem and Polyethylene glycol. Irritable bowel syndrome [DD91] [18]
Bupropion DM5PCS7 Major Increased risk of lowers seizure threshold by the combination of Meropenem and Bupropion. Nicotine use disorder [6C4A] [19]

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 Meropenem FDA Label
3 BDDCS applied to over 900 drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 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
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Characterization of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, and meropenem as substrates of human renal transporters. Drug Metab Pharmacokinet. 2007 Feb 25;22(1):41-7.
8 Genomic characterization of an extensively-drug resistance Salmonella enterica serotype Indiana strain harboring bla NDM-1 gene isolated from a chicken carcass in China. Microbiol Res. 2017 Nov;204:48-54.
9 FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan. J Antimicrob Chemother. 2018 Nov 1;73(11):2969-2972.
10 Prevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolates. Clin Microbiol Infect. 2019 Sep;25(9):1156.e9-1156.e13.
11 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.
12 Chronic colitis after Aeromonas infection. Gut. 1989 May;30(5):686-90. Case Reports
13 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.
14 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.
15 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
16 Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
17 Bax RP, Bastain W, Featherstone A, Wilkinson DM, Hutchison M, Haworth SJ "The pharmacokinetics of meropenem in volunteers." J Antimicrob Chemother 24(suppl a (1989): 311-20. [PMID: 2808215]
18 Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
19 Product Information. Wellbutrin XL (buPROPion). GlaxoSmithKline, Philadelphia, PA.