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Identification
NameCarbenicillin
Accession NumberDB00578  (APRD00846)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
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
alpha-Carboxybenzylpencillin
alpha-Phenyl(carboxymethylpenicillin)
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
External Identifiers
  • BRL 2064
  • CP 15639-2
  • NSC 111071
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CarbenicillinPolfa Tarchomin
PyopenGlaxoSmithKline
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Carbenicillin disodium
ThumbNot applicableDBSALT001334
Categories
UNIIG42ZU72N5G
CAS number4697-36-3
WeightAverage: 378.4
Monoisotopic: 378.088557008
Chemical FormulaC17H18N2O6S
InChI KeyInChIKey=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)[[email protected]]2NC(=O)C(C(O)=O)C1=CC=CC=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as penicillins. These are organic compounds containing the penicillin core structure, which is structurally characterized by a penam ring bearing two methyl groups at position 2, and an amide group at position 6 [starting from the sulfur atom at position 1].
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentPenicillins
Alternative Parents
Substituents
  • Penicillin
  • N-acyl-alpha amino acid or derivatives
  • Phenylacetamide
  • Phenylpropylamine
  • Phenylacetate
  • Alpha-amino acid or derivatives
  • Benzenoid
  • 1,3-dicarbonyl compound
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Thiazolidine
  • Tertiary carboxylic acid amide
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Hemithioaminal
  • Thioether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of bacteria.
PharmacodynamicsCarbenicillin 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 actionFree 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.
Related Articles
AbsorptionRapidly absorbed from the small intestine following oral administration. Oral bioavailability is 30 to 40%.
Volume of distributionNot Available
Protein binding30 to 60%
Metabolism

Minimal.

Route of eliminationNot Available
Half life1 hour
ClearanceNot Available
ToxicityCarbenicillin 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.
Affected organisms
  • Enteric bacteria and other eubacteria
  • Gram-negative Bacteria
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Proteus mirabilis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Roerig div pfizer inc
  • Glaxosmithkline
Packagers
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesJ01CA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolCarbenicillin may increase the anticoagulant activities of Acenocoumarol.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Carbenicillin.
BiotinThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Biotin.
DemeclocyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Demeclocycline.
DoxycyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Doxycycline.
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Carbenicillin.
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Carbenicillin.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Carbenicillin.
MinocyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Minocycline.
Mycophenolate mofetilThe serum concentration of the active metabolites of Mycophenolate mofetil can be reduced when Mycophenolate mofetil is used in combination with Carbenicillin resulting in a loss in efficacy.
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Carbenicillin resulting in a loss in efficacy.
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Carbenicillin.
ProbenecidThe serum concentration of Carbenicillin can be increased when it is combined with Probenecid.
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Carbenicillin.
TetracyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Tetracycline.
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Carbenicillin.
WarfarinCarbenicillin may increase the anticoagulant activities of Warfarin.
Food Interactions
  • Take on an empty stomach.

Targets

1. Penicillin-binding protein
Kind
Protein group
Organism
Gram positive and gram negative bacteria
Pharmacological action
yes
Actions
inhibitor
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. [PubMed:20974151 ]

Enzymes

Kind
Protein
Organism
Human
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 response.
Gene Name:
PLA2G4A
Uniprot ID:
P47712
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. [PubMed:541266 ]

Transporters

Kind
Protein
Organism
Human
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
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. [PubMed:10411577 ]
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Drug created on June 13, 2005 07:24 / Updated on November 26, 2015 17:14