CARBENICILLIN PHENYL

First approved in 1970

Details

Stereochemistry	EPIMERIC
Molecular Formula	C23H22N2O6S
Molecular Weight	454.496
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C(C(=O)OC3=CC=CC=C3)C4=CC=CC=C4)C(O)=O

InChI

InChIKey=NZDASSHFKWDBBU-KVMCETHSSA-N

InChI=1S/C23H22N2O6S/c1-23(2)17(21(28)29)25-19(27)16(20(25)32-23)24-18(26)15(13-9-5-3-6-10-13)22(30)31-14-11-7-4-8-12-14/h3-12,15-17,20H,1-2H3,(H,24,26)(H,28,29)/t15?,16-,17+,20-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://link.springer.com/chapter/10.1007%2F978-1-4684-3126-1_11https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/21771 and http://www.ncbi.nlm.nih.gov/pubmed/789326

Geocillin, a trade name is the sodium salt of the indanyl ester of carbenicillin disodium, which used to treat acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of bacteria. In addition, Geocillin was also indicated in the treatment of prostatitis due to susceptible strains of the following organisms: Escherichia coli; Enterococcus (S. faecalis); Proteus mirabilis; Enterobacter sp. Free carbenicillin is the predominant pharmacologically active fraction of Geocillin. After absorption, Geocillin is rapidly converted to carbenicillin by hydrolysis of the ester linkage. 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. In 2008 Pfizer has decided to discontinue the manufacturing of Geocillin (carbenicillin indanyl sodium)

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Neprilysin 29 Target ID: CHEMBL1944 Sources: http://www.ncbi.nlm.nih.gov/pubmed/1284433	Inhibitor 8297	0.18 µM [Ki]
Escherichia coli growth 23 Target ID: Escherichia coli growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/21771	Inhibitor 8297
Staphylococcus aureus growth 27 Target ID: Staphylococcus aureus growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/21771	Inhibitor 8297
Streptococcus pneumoniae growth 20 Target ID: Streptococcus pneumoniae growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/21771	Inhibitor 8297
Pseudomonas aeruginosa growth 10 Target ID: Pseudomonas aeruginosa growth Sources: http://www.ncbi.nlm.nih.gov/pubmed/21771	Inhibitor 8297
Bacterial penicillin-binding protein 233 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20974151	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.ncbi.nlm.nih.gov/pubmed/7116379	Curative	Approved 8429	Uticillin Approved Use Indications: urinary tract infections
Acute and chronic infections of the upper and lower urinary tract 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf	Curative	Approved 8429	GEOCILLIN Approved Use Geocillin (carbenicillin indanyl sodium) is indicated in the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of the following organisms: Escherichia coli; Proteus mirabilis; Morganella morganii (formerly Proteus morganii); Providencia rettgeri (formerly Proteus rettgeri); Proteus vulgaris; Pseudomonas Enterobacter; Enterococci. Geocillin is also indicated in the treatment of prostatitis due to susceptible strains of the following organisms: Escherichia coli; Enterococcus (S. faecalis); Proteus mirabilis; Enterobacter sp. WHEN HIGH AND RAPID BLOOD AND URINE LEVELS OF ANTIBIOTIC ARE INDICATED, THERAPY WITH GEOPEN (CARBENICILLIN DISODIUM) SHOULD BE INITIATED BY PARENTERAL ADMINISTRATION FOLLOWED, AT THE PHYSICIAN’S DISCRETION, BY ORAL THERAPY. To reduce the development of drug-resistant bacteria and maintain effectiveness of Geocillin and other antibacterial drugs, Geocillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1972
Prostatitis 25 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf	Curative	Approved 8429	GEOCILLIN Approved Use Geocillin (carbenicillin indanyl sodium) is indicated in the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of the following organisms: Escherichia coli; Proteus mirabilis; Morganella morganii (formerly Proteus morganii); Providencia rettgeri (formerly Proteus rettgeri); Proteus vulgaris; Pseudomonas Enterobacter; Enterococci. Geocillin is also indicated in the treatment of prostatitis due to susceptible strains of the following organisms: Escherichia coli; Enterococcus (S. faecalis); Proteus mirabilis; Enterobacter sp. WHEN HIGH AND RAPID BLOOD AND URINE LEVELS OF ANTIBIOTIC ARE INDICATED, THERAPY WITH GEOPEN (CARBENICILLIN DISODIUM) SHOULD BE INITIATED BY PARENTERAL ADMINISTRATION FOLLOWED, AT THE PHYSICIAN’S DISCRETION, BY ORAL THERAPY. To reduce the development of drug-resistant bacteria and maintain effectiveness of Geocillin and other antibacterial drugs, Geocillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1972

C_max

Value	Dose	Co-administered	Analyte	Population
6.5 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf	382 mg single, oral dose: 382 mg route of administration: Oral experiment type: SINGLE co-administered:		CARBENICILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
16 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf	382 mg single, oral dose: 382 mg route of administration: Oral experiment type: SINGLE co-administered:		CARBENICILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050435s009lbl.pdf	382 mg single, oral dose: 382 mg route of administration: Oral experiment type: SINGLE co-administered:		CARBENICILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 g 4 times / day steady, intravenous Dose: 5 g, 4 times / day Route: intravenous Route: steady Dose: 5 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/622610/	unhealthy, 57 years Health Status: unhealthy Condition: interstitial nephritis Age Group: 57 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/622610/	Other AEs: Nephrotoxicity... Other AEs: Nephrotoxicity (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/622610/

AEs

AE	Significance	Dose	Population
Nephrotoxicity	1 patient	5 g 4 times / day steady, intravenous Dose: 5 g, 4 times / day Route: intravenous Route: steady Dose: 5 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/622610/	unhealthy, 57 years Health Status: unhealthy Condition: interstitial nephritis Age Group: 57 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/622610/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OAT1 326

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8285614/, https://pubmed.ncbi.nlm.nih.gov/12697641/	yes		yes (co-administration study) Comment: When coadministrated with Probenecid (OAT inhibitor), Carbenicillin CLr was significantlly reduced. Sources: https://pubmed.ncbi.nlm.nih.gov/8285614/, https://pubmed.ncbi.nlm.nih.gov/12697641/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3393	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3393
ChemicalBook	CB0243304	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0243304
MolPort	MolPort-006-116-396	https://www.molport.com/shop/molecule-link/MolPort-006-116-396
eMolecules	535811	https://www.emolecules.com/cgi-bin/more?vid=535811

PubMed

Title	Date	PubMed
Carbenicillin prodrugs: stability kinetics of alpha-phenyl and alpha-indanyl esters in aqueous solution.	1979 Oct	583161
Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin.	1994 Apr 15	8200509
Changes in antibiotic resistance in equine bacterial ulcerative keratitis (1991-2000): 65 horses.	2003 Dec	14641828
[Optimization of T-dNA insertional mutagenesis and analysis of mutants of Magnaporthe grisea].	2003 Jul	15969057
Antimicrobial susceptibility pattern of clinical isolates of non-fermentative bacteria.	2003 Jul	15025332
Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients.	2003 Oct	12974973
Molecular characterization of plasmids with antimicrobial resistant genes in avian isolates of Pasteurella multocida.	2003 Oct-Dec	14708986
Shewanella waksmanii sp. nov., isolated from a sipuncula (Phascolosoma japonicum).	2003 Sep	13130035
Thermophile-specific proteins: the gene product of aq_1292 from Aquifex aeolicus is an NTPase.	2003 Sep 23	14503925
Evaluation of a simple carrier molecule to enhance drug penetration of dermal layers by utilizing multivariate methods, structure property correlations, and continuous system modeling.	2004	15789972
[Pseudomonas aeruginosa--a significant hospital pathogen and resistance to carbapenem].	2004	15700688
Genome-wide mutagenesis of Zea mays L. using RescueMu transposons.	2004	15461800
Investigation of Burkholderia cepacia nosocomial outbreak with high fatality in patients suffering from diseases other than cystic fibrosis.	2004	15119360
Self-transmissible antibiotic resistance to ampicillin, streptomycin, and tetracyclin found in Escherichia coli isolates from contaminated drinking water.	2004	15055932
Penicillin derivatives induce chemical structure-dependent root development, and application for plant transformation.	2004 Apr	14727052
Vibrio vulnificus in Taiwan.	2004 Aug	15496235
Interaction studies on proteins encoded by the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis.	2004 Dec	15668773
Distribution and characterization of Campylobacter spp. from Russian poultry.	2004 Feb	14968953
Staphylococcus aureus and Escherichia hermanii in diabetes patient.	2004 Jul	15338542
Molecular dissection of the human antibody response to the structural repeat epitope of Plasmodium falciparum sporozoite from a protected donor.	2004 Jul 29	15283866
Prevalence, antibiotic susceptibility, and virulence factors of Yersinia enterocolitica and related species from ready-to-eat vegetables available in Korea.	2004 Jun	15222537
Serratia marcescens internalization and replication in human bladder epithelial cells.	2004 Jun 9	15189566
Bacterial variations on the methionine salvage pathway.	2004 Mar 4	15102328
Xylella fastidiosa subspecies: X. fastidiosa subsp. [correction] fastidiosa [correction] subsp. nov., X. fastidiosa subsp. multiplex subsp. nov., and X. fastidiosa subsp. pauca subsp. nov.	2004 May	15214634
Symbiotic innovation in the oxymonad Streblomastix strix.	2004 May-Jun	15218697
Dictyostelium myosin bipolar thick filament formation: importance of charge and specific domains of the myosin rod.	2004 Nov	15492777
Mycobacterium tuberculosis from chronic murine infections that grows in liquid but not on solid medium.	2004 Nov 17	15548322
Functional characterization in Caenorhabditis elegans of transmembrane worm-human orthologs.	2004 Nov 8	15533247
Resistance to beta-lactam antibiotics in Aeromonas hydrophila isolated from rainbow trout (Oncorhynchus mykiss).	2004 Sep	15492935
Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.	2004 Sep 14	15342186
Early detection of breast cancer based on gene-expression patterns in peripheral blood cells.	2005	16168108
Common antimicrobial resistance patterns, biotypes and serotypes found among Pseudomonas aeruginosa isolates from patient's stools and drinking water sources in Jordan.	2005 Apr	15920903
Efficient genetic transformation of Sorghum using a visual screening marker.	2005 Apr	15838555
Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans.	2005 Feb	15719061
New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.	2005 Jul	16103914
Characterization of Pseudomonas aeruginosa isolated from chronically infected children with cystic fibrosis in India.	2005 Jul 21	16033658
Development of ERK Activity Sensor, an in vitro, FRET-based sensor of Extracellular Regulated Kinase activity.	2005 Jul 5	15998468
Epidemic strain Shigella dysenteriae Type 1 Dt66 encodes several drug resistances by chromosome.	2005 Jul-Aug	15950082
Cognate peptide-receptor ligand mapping by directed phage display.	2005 Jun 17	15963231
Selectivity of ertapenem for Pseudomonas aeruginosa mutants cross-resistant to other carbapenems.	2005 Mar	15705643
[Antibiotic resistance of shigellae and rationale for etiotropic therapy of Shigella infections].	2005 Mar-Apr	15881945
Antimicrobial responses of Yersinia enterocolitica isolates in comparison to other commonly encountered bacteria that causes diarrhoea.	2005 May	16119753
Infrared and Raman microspectroscopy of foreign materials in tissue specimens.	2005 May	15820906
Characterization of antimicrobial resistance and class 1 integrons found in Escherichia coli isolates from humans and animals in Korea.	2005 May	15761064
Occurrence of antibiotic and metal resistance in bacteria from organs of river fish.	2005 May	15721889
An improved method for rapid generation of unmarked Pseudomonas aeruginosa deletion mutants.	2005 May 23	15907219
A combined approach exploring gene function based on worm-human orthology.	2005 May 6	15877817
Functional genomic analysis of C. elegans molting.	2005 Oct	16122351
Uncoupling of longevity and telomere length in C. elegans.	2005 Sep	16151516
Changes in patterns of antimicrobial susceptibility and class 1 integron carriage among Escherichia coli isolates.	2005 Sep	16131822

Patents

Sample Use Guides

In Vivo Use Guide

500 mg every 8 h for 7 days .

Route of Administration: Oral

In Vitro Use Guide

Carfecillin inhibited Staphylococcus aureus growth with MIC 0.25 ug/ml

Name

Type

Language

CARBENICILLIN PHENYL

Common Name

English

N-(2-CARBOXY-3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLO(3.2.0)HEPT-6-YL)-2-PHENYLMALONAMIC ACID 1-PHENYL ESTER

Systematic Name

English

carfecillin [INN]

Common Name

English

CARFECILLIN [JAN]

Common Name

English

Carfecillin [WHO-DD]

Common Name

English

4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 6-((1,3-DIOXO-3-PHENOXY-2-PHENYLPROPYL)AMINO)-3,3-DIMETHYL-7-OXO-, (2S-(2.ALPHA.,5.ALPHA.,6.BETA.))

Common Name

English

CARFECILLIN

Official Name

English

Classification Tree Code System Code

WHO-VATC

QG01AA08