Details of the Drug

General Information of Drug (ID: DMLEDNK)

• Drug Name: Carbenicillin
• Synonyms: CBPC; Carbenicilina; Carbenicillina; Carbenicilline; Carbenicillinum; Carboxybenzylpenicillin; Pyopen; Carbenicillina [DCIT]; Carboxybenzyl Penicillin; Carboxybenzylpenicillin acid; Alpha-Carboxybenzylpencillin; Alpha-Carboxybenzylpenicillin solution; Carbenicilina [INN-Spanish]; Carbenicillin (INN); Carbenicillin [INN:BAN]; Carbenicilline [INN-French]; Carbenicillinum [INN-Latin]; Alpha-Phenyl(carboxymethylpenicillin); N-(2-Carboxy-3,3-dimethyl-7-oxo-4-thia-azabicyclo(3.2.0)hept-6-yl)-2-phenylmalonamic acid;N-(2-carboxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)hept-6-yl)-2-phenylmalonamic acid; (2S,5R,6R)-6-[(3-hydroxy-3-oxo-2-phenylpropanoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[carboxy(phenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 6-(alpha-Carboxyphenylacetamido)penicillanic acid; 6beta-(2-carboxy-2-phenylacetamido)-2,2-dimethylpenam-3alpha-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Infection of the upper and lower urinary tract	GC08	Approved	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 378.4
  Topological Polar Surface Area (xlogp); 1.1
  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 3: high solubility and low permeability [2]
  Bioavailability: The bioavailability of drug is 30-40% [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.9 mL/min/kg [4]
  Elimination: 82% 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 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 115.37 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.52% [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 0.17 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [2]
• Chemical Identifiers:
  Formula: C17H18N2O6S
  IUPAC Name: (2S,5R,6R)-6-[(2-carboxy-2-phenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  Canonical SMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)C(C3=CC=CC=C3)C(=O)O)C(=O)O)C
  InChI: InChI=1S/C17H18N2O6S/c1-17(2)11(16(24)25)19-13(21)10(14(19)26-17)18-12(20)9(15(22)23)8-6-4-3-5-7-8/h3-7,9-11,14H,1-2H3,(H,18,20)(H,22,23)(H,24,25)/t9?,10-,11+,14-/m1/s1
  InChIKey: FPPNZSSZRUTDAP-UWFZAAFLSA-N
• Cross-matching ID:
  PubChem CID: 20824
  ChEBI ID: CHEBI:3393
  CAS Number: 4697-36-3
  DrugBank ID: DB00578
  TTD ID: D02TBI
  VARIDT ID: DR00995
  INTEDE ID: DR2390

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	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
N-acylhomoserine lactone acylase (lacA)	DEIU0XN	A0A0A1VBK6_9BURK	Substrate	[7]
PenA beta-lactamase (penA1)	DE2ARDZ	O08350_BURCE	Substrate	[8]
Beta-lactamase (blaB)	DEF01WC	A0A3S4HKA9_CHRVL	Substrate	[9]
Beta-lactamase (blaB)	DEXB2A9	A0A379CPC3_PLESH	Substrate	[10], [11]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Anisindione	DM2C48U	Moderate	Increased risk of bleeding by the combination of Carbenicillin and Anisindione.	Coagulation defect [3B10]	[21]
Mycophenolic acid	DMU65NK	Moderate	Altered absorption of Carbenicillin due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[22]
Probenecid	DMMFWOJ	Minor	Decreased elimination of Carbenicillin caused by Probenecid mediated competitive inhibition of renal tubular secretion.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[23]
Warfarin	DMJYCVW	Moderate	Increased risk of bleeding by the combination of Carbenicillin and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[21]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Carbenicillin due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[22]

References

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• [2] BDDCS applied to over 900 drugs
• [3] 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.
• [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] 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.
• [7] A novel quorum-quenching N-acylhomoserine lactone acylase from Acidovorax sp. strain MR-S7 mediates antibiotic resistance. Appl Environ Microbiol. 2017 Jun 16;83(13). pii: e00080-17.
• [8] Characterization of the penA and penR genes of Burkholderia cepacia 249 which encode the chromosomal class A penicillinase and its LysR-type transcriptional regulator. Antimicrob Agents Chemother. 1997 Nov;41(11):2399-405.
• [9] Beta-lactamase activity in Chromobacterium violaceum. J Infect Dis. 1976 Sep;134(3):290-3.
• [10] Beta-lactamase expression in Plesiomonas shigelloides. J Antimicrob Chemother. 2000 Jun;45(6):877-80.
• [11] Identification and functional characterization of arylamine N-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid. J Bacteriol. 2001 Jun;183(11):3417-27.
• [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] In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enter... J Infect Dis. 2004 Dec 15;190(12):2162-6.
• [21] Alexander DP, Russo ME, Fohrman DE, Rothstein G "Nafcillin-induced platelet dysfunction and bleeding." Antimicrob Agents Chemother 23 (1983): 59-62. [PMID: 6830209]
• [22] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [23] Allen MB, Fitzpatrick RW, Barratt A, Cole RB "The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis." Respir Med 84 (1990): 143-6. [PMID: 2371437]