Carbenicillin

Identification

Generic Name
Carbenicillin
DrugBank Accession Number
DB00578
Background

Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 378.4
Monoisotopic: 378.088557008
Chemical Formula
C17H18N2O6S
Synonyms
  • (2S,5R,6R)-6-{[carboxy(phenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • Carbenicilina
  • Carbenicillin
  • Carbenicilline
  • Carbenicillinum
  • Carboxybenzylpenicillin
  • CBPC
  • N-(2-carboxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)hept-6-yl)-2-phenylmalonamic acid
  • α-carboxybenzylpencillin
  • α-phenyl(carboxymethylpenicillin)
External IDs
  • BRL 2064
  • CP 15639-2
  • NSC 111071

Pharmacology

Indication

For the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of bacteria.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantial in vitro activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas species, Providencia rettgeri, Enterobacter species, and Enterococci (S. faecalis).

Mechanism of action

Free carbenicillin is the predominant pharmacologically active fraction of the salt. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria. Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that carbenicillin interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein
inhibitor
Gram positive and gram negative bacteria
UBeta-lactamase Toho-1
substrate
Escherichia coli
Absorption

Rapidly absorbed from the small intestine following oral administration. Oral bioavailability is 30 to 40%.

Volume of distribution

Not Available

Protein binding

30 to 60%

Metabolism

Minimal.

Route of elimination

Not Available

Half-life

1 hour

Clearance

Not Available

Adverse Effects
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Toxicity

Carbenicillin blood levels achievable are very low, and toxic reactions as a function of overdosage should not occur systematically. The oral LD50 in mice is 3,600 mg/kg, in rats 2,000 mg/kg, and in dogs is in excess of 500 mg/kg. The lethal human dose is not known. Symptoms of overdose include diarrhea, nausea, stomach upset, and vomiting.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcemetacinAcemetacin may decrease the excretion rate of Carbenicillin which could result in a higher serum level.
AcenocoumarolCarbenicillin may increase the anticoagulant activities of Acenocoumarol.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Carbenicillin.
Adefovir dipivoxilThe excretion of Adefovir dipivoxil can be decreased when combined with Carbenicillin.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Carbenicillin is combined with Ambroxol.
Food Interactions
  • Take on an empty stomach.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Carbenicillin disodium9TS4B3H2614800-94-6RTYJTGSCYUUYAL-YCAHSCEMSA-L
International/Other Brands
Carbenicillin (Polfa Tarchomin) / Pyopen (GlaxoSmithKline)

Categories

ATC Codes
J01CR50 — Combinations of penicillinsJ01CA03 — Carbenicillin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Penicillins / N-acyl-alpha amino acids and derivatives / Phenylacetamides / 1,3-dicarbonyl compounds / Dicarboxylic acids and derivatives / Thiazolidines / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Azetidines / Thiohemiaminal derivatives
show 7 more
Substituents
1,3-dicarbonyl compound / Alpha-amino acid or derivatives / Alpha-dipeptide / Aromatic heteropolycyclic compound / Azacycle / Azetidine / Benzenoid / Beta-lactam / Carbonyl group / Carboxamide group
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:3393)
Affected organisms
  • Enteric bacteria and other eubacteria
  • Gram-negative Bacteria
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Proteus mirabilis

Chemical Identifiers

UNII
G42ZU72N5G
CAS number
4697-36-3
InChI Key
FPPNZSSZRUTDAP-UWFZAAFLSA-N
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
IUPAC Name
(2S,5R,6R)-6-(2-carboxy-2-phenylacetamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C(C(O)=O)C1=CC=CC=C1)C(O)=O

References

Synthesis Reference

Brain, E.G. and Nayler, J.H.C.; US. Patents 3,282,926; November 1,1966 and 3,492,291; January 27,1970; both assigned to Beecham Group Limited, England.

General References
Not Available
Human Metabolome Database
HMDB0014717
KEGG Drug
D07614
KEGG Compound
C06869
PubChem Compound
20824
PubChem Substance
46505653
ChemSpider
19599
RxNav
2015
ChEBI
3393
ChEMBL
CHEMBL1214
Therapeutic Targets Database
DAP000438
PharmGKB
PA448788
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbenicillin
MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Roerig div pfizer inc
  • Glaxosmithkline
Packagers
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility451 mg/LNot Available
logP1.13HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.39 mg/mLALOGPS
logP1.13ALOGPS
logP0.82Chemaxon
logS-3ALOGPS
pKa (Strongest Acidic)3.11Chemaxon
pKa (Strongest Basic)-6.3Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area124.01 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity90.82 m3·mol-1Chemaxon
Polarizability36.39 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9112
Blood Brain Barrier-0.9954
Caco-2 permeable-0.7812
P-glycoprotein substrateSubstrate0.5274
P-glycoprotein inhibitor INon-inhibitor0.9447
P-glycoprotein inhibitor IINon-inhibitor0.9872
Renal organic cation transporterNon-inhibitor0.962
CYP450 2C9 substrateNon-substrate0.7684
CYP450 2D6 substrateNon-substrate0.8611
CYP450 3A4 substrateNon-substrate0.5946
CYP450 1A2 substrateNon-inhibitor0.8778
CYP450 2C9 inhibitorNon-inhibitor0.9259
CYP450 2D6 inhibitorNon-inhibitor0.935
CYP450 2C19 inhibitorNon-inhibitor0.9206
CYP450 3A4 inhibitorNon-inhibitor0.8921
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9761
Ames testNon AMES toxic0.8884
CarcinogenicityNon-carcinogens0.6178
BiodegradationNot ready biodegradable0.976
Rat acute toxicity1.4599 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9997
hERG inhibition (predictor II)Non-inhibitor0.9091
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-000f-9648000000-75c4ae9c8d8548759c79
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-08ml-0941000000-dd04761aba676e737365
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0093000000-2481d8576e383313ecfa
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0910000000-5e16937a715baee100d2
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0016-9774000000-fce5db20fc35ce747364
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014l-1900000000-9fcde5d9a40519e2fca4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9626000000-3b8a7fd71c7606208706
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-190.0361556
predicted
DarkChem Lite v0.1.0
[M-H]-182.77989
predicted
DeepCCS 1.0 (2019)
[M+H]+191.4709556
predicted
DarkChem Lite v0.1.0
[M+H]+185.17546
predicted
DeepCCS 1.0 (2019)
[M+Na]+190.5526556
predicted
DarkChem Lite v0.1.0
[M+Na]+191.08798
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Gram positive and gram negative bacteria
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.

Components:
References
  1. Sainsbury S, Bird L, Rao V, Shepherd SM, Stuart DI, Hunter WN, Owens RJ, Ren J: Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: comparison of native and antibiotic-bound forms. J Mol Biol. 2011 Jan 7;405(1):173-84. doi: 10.1016/j.jmb.2010.10.024. Epub 2010 Oct 23. [Article]
Kind
Protein
Organism
Escherichia coli
Pharmacological action
Unknown
Actions
Substrate
General Function
Beta-lactamase activity
Specific Function
Has strong cefotaxime-hydrolyzing activity.
Gene Name
bla
Uniprot ID
Q47066
Uniprot Name
Beta-lactamase Toho-1
Molecular Weight
31446.6 Da
References
  1. Ishii Y, Ohno A, Taguchi H, Imajo S, Ishiguro M, Matsuzawa H: Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A beta-lactamase isolated from Escherichia coli. Antimicrob Agents Chemother. 1995 Oct;39(10):2269-75. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
References
  1. Sugatani J, Saito K, Honjo I: In vitro actions of some antibiotics on phospholipases. J Antibiot (Tokyo). 1979 Jul;32(7):734-9. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:53