CARBENICILLIN PHENYL SODIUM

First approved in 1970

Details

Stereochemistry	MIXED
Molecular Formula	C23H21N2O6S.Na
Molecular Weight	476.477
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of CARBENICILLIN PHENYL SODIUM

Structure Search

SMILES

[Na+].[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=JXSBZDNBNJTHBJ-JPZUGYNPSA-M

InChI=1S/C23H22N2O6S.Na/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);/q;+1/p-1/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
Therapeutic efficacy of tobramycin--a clinical and laboratory evaluation.	1975 Dec	1107297
Bleeding in uremic patients after carbenicillin.	1976 Aug 31	1036800
Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin.	1994 Apr 15	8200509
[Improvement of transformation frequency of rice mediated by Agrobacterium].	2001	11329877
Generation of class-selective monoclonal antibodies against the penicillin group.	2001 Jul	11453774
Probing the penicillin sidechain selectivity of recombinant deacetoxycephalosporin C synthase.	2001 May	11437242
In vitro susceptibility to 15 antibiotics of vibrios isolated from penaeid shrimps in Northwestern Mexico.	2001 May	11337225
Characterization of a putative RND-type efflux system in Agrobacterium tumefaciens.	2001 May 30	11404022
Epidemiologic Study of Pseudomonas aeruginosa in critical patients and reservoirs.	2001 May-Jun	11395191
Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms.	2002 Apr 15	11914992
Growth and differentiation of transgenic callus regulated by phytohormones and antibiotics in transformation of loblolly pine.	2002 Feb	11902001
Characterization of cefotaxime-resistant Escherichia coli isolates from a nosocomial outbreak at three geriatric hospitals.	2002 Jun	12111569
Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their resistance to antibiotics.	2002 Jun	12052372
Interaction of the Yersinia pestis type III regulatory proteins LcrG and LcrV occurs at a hydrophobic interface.	2002 Jun 28	12102728
DNA-DNA reassociation and phenotypic data indicate synonymy between Aeromonas enteropelogenes Schubert et al. 1990 and Aeromonas trota Carnahan et al. 1991.	2002 Nov	12508855
Establishment of a highly efficient transformation system for pepper (Capsicum annuum L.).	2003 Apr	12789523
Surprisingly fast disappearance of beta-lactam selection pressure in cultivation as detected with novel biosensing approaches.	2003 Apr	12609721
Catalytic properties of an endogenous beta-lactamase responsible for the resistance of Azospirillum lipoferum to beta-lactam antibiotics.	2003 Feb	12624206
[Optimization of T-dNA insertional mutagenesis and analysis of mutants of Magnaporthe grisea].	2003 Jul	15969057
Molecular characterisation and antimicrobial resistance of Vibrio vulnificus and Vibrio alginolyticus isolated from mussels (Mytilus galloprovincialis).	2003 Mar	12747419
Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients.	2003 Oct	12974973
The susceptibility of ionophore-resistant Clostridium aminophilum F to other antibiotics.	2003 Oct	12951349
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
Investigation of Burkholderia cepacia nosocomial outbreak with high fatality in patients suffering from diseases other than cystic fibrosis.	2004	15119360
Penicillin derivatives induce chemical structure-dependent root development, and application for plant transformation.	2004 Apr	14727052
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
Resistance to beta-lactam antibiotics in Aeromonas hydrophila isolated from rainbow trout (Oncorhynchus mykiss).	2004 Sep	15492935
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
Selectivity of ertapenem for Pseudomonas aeruginosa mutants cross-resistant to other carbapenems.	2005 Mar	15705643
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
Functional genomic analysis of C. elegans molting.	2005 Oct	16122351

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 SODIUM

Official Name

English

CARBENICILLIN PHENYL SODIUM [MI]

Common Name

English

CARFECILLIN SODIUM [MART.]

Common Name

English

CARBENICILLIN PHENYL SODIUM [USAN]

Common Name

English

Carfecillin sodium [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-, MONOSODIUM SALT, (2S-(2.ALPHA.,5.ALPHA.,6.BETA.))

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 sodium salt

Common Name

English

CARFECILLIN SODIUM

Common Name

English

BRL-3475

Code

English

CARFECILLIN SODIUM [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1500