Identification

Name
Carbenicillin
Accession Number
DB00578  (APRD00846)
Type
Small Molecule
Groups
Approved, Investigational
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 IDs
BRL 2064 / CP 15639-2 / NSC 111071
Product Ingredients
IngredientUNIICASInChI Key
Carbenicillin disodium9TS4B3H2614800-94-6RTYJTGSCYUUYAL-YCAHSCEMSA-L
International/Other Brands
Carbenicillin (Polfa Tarchomin) / Pyopen (GlaxoSmithKline)
Categories
UNII
G42ZU72N5G
CAS number
4697-36-3
Weight
Average: 378.4
Monoisotopic: 378.088557008
Chemical Formula
C17H18N2O6S
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][[email protected]]12SC(C)(C)[[email protected]@H](N1C(=O)[[email protected]]2NC(=O)C(C(O)=O)C1=CC=CC=C1)C(O)=O

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.

Structured Indications
Not Available
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
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
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.

Affected organisms
  • Enteric bacteria and other eubacteria
  • Gram-negative Bacteria
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Proteus mirabilis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCarbenicillin may increase the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Carbenicillin.Investigational
AldoxorubicinThe serum concentration of Aldoxorubicin can be decreased when it is combined with Carbenicillin.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Carbenicillin.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Carbenicillin.Approved, Investigational
AnnamycinThe serum concentration of Annamycin can be decreased when it is combined with Carbenicillin.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Carbenicillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Carbenicillin.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Carbenicillin.Investigational
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Carbenicillin.Experimental
ChlortetracyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Chlortetracycline.Approved, Investigational, Vet Approved
ClorindioneCarbenicillin may increase the anticoagulant activities of Clorindione.Experimental
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Carbenicillin.Approved
DemeclocyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Demeclocycline.Approved
DibekacinThe serum concentration of Dibekacin can be decreased when it is combined with Carbenicillin.Experimental
DicoumarolCarbenicillin may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Carbenicillin.Investigational, Vet Approved
DiphenadioneCarbenicillin may increase the anticoagulant activities of Diphenadione.Experimental
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Carbenicillin.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Carbenicillin.Approved
Ethyl biscoumacetateCarbenicillin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCarbenicillin may increase the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Carbenicillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Carbenicillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Carbenicillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Carbenicillin.Experimental
GPX-150The serum concentration of GPX-150 can be decreased when it is combined with Carbenicillin.Investigational
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Carbenicillin.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Carbenicillin.Approved
IsepamicinThe serum concentration of Isepamicin can be decreased when it is combined with Carbenicillin.Experimental
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Carbenicillin.Approved, Investigational, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Carbenicillin.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Carbenicillin.Approved
MicronomicinThe serum concentration of Micronomicin can be decreased when it is combined with Carbenicillin.Experimental
MinocyclineThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Minocycline.Approved, Investigational
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.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Carbenicillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Carbenicillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Carbenicillin.Approved, Investigational
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Carbenicillin.Approved, Investigational
PhenindioneCarbenicillin may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCarbenicillin may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Carbenicillin.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Carbenicillin.Investigational
PlazomicinThe serum concentration of Plazomicin can be decreased when it is combined with Carbenicillin.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Carbenicillin.Approved, Investigational, Withdrawn
ProbenecidThe serum concentration of Carbenicillin can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Carbenicillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Carbenicillin.Approved, Investigational
SabarubicinThe serum concentration of Sabarubicin can be decreased when it is combined with Carbenicillin.Investigational
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Carbenicillin.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Carbenicillin.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Carbenicillin.Approved, Investigational, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Carbenicillin.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Carbenicillin.Approved
TioclomarolCarbenicillin may increase the anticoagulant activities of Tioclomarol.Experimental
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Carbenicillin.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Carbenicillin.Approved
WarfarinCarbenicillin may increase the anticoagulant activities of Warfarin.Approved
Zoptarelin doxorubicinThe serum concentration of Zoptarelin doxorubicin can be decreased when it is combined with Carbenicillin.Investigational
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Carbenicillin.Experimental
Food Interactions
  • Take on an empty stomach.

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
External Links
Human Metabolome Database
HMDB14717
KEGG Compound
C06869
PubChem Compound
20824
PubChem Substance
46505653
ChemSpider
19599
ChEBI
3393
ChEMBL
CHEMBL1214
Therapeutic Targets Database
DAP000438
PharmGKB
PA448788
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbenicillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CA03 — Carbenicillin
MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Alpha-dipeptide / Penicillin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Phenylacetamide / Penam / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / 1,3-dicarbonyl compound / Benzenoid
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:3393)

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...
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. [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 ...
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. [PubMed:10411577]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:22