CEFOPERAZONE

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H27N9O8S2
Molecular Weight	645.667
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)[C@H](NC(=O)N4CCN(CC)C(=O)C4=O)C5=CC=C(O)C=C5)C(O)=O

InChI

InChIKey=GCFBRXLSHGKWDP-XCGNWRKASA-N

InChI=1S/C25H27N9O8S2/c1-3-32-8-9-33(21(39)20(32)38)24(42)27-15(12-4-6-14(35)7-5-12)18(36)26-16-19(37)34-17(23(40)41)13(10-43-22(16)34)11-44-25-28-29-30-31(25)2/h4-7,15-16,22,35H,3,8-11H2,1-2H3,(H,26,36)(H,27,42)(H,40,41)/t15-,16-,22-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C25H27N9O8S2
Molecular Weight	645.667
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/cefobid-drug.htm

Cefoperazone (marketed under the name Cefobid) is a third-generation cephalosporin antibiotic. Cefoperazone has a broad spectrum of activity: Respiratory Tract Infections caused by S. pneumoniae, H. influenzae, S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes (Group A beta-hemolytic streptococci), P. aeruginosa, Klebsiella pneumoniae, E. coli, Proteus mirabilis, and Enterobacter species. Peritonitis and Other Intra-abdominal Infections caused by E. coli, P. aeruginosa, and anaerobic gram-negative bacilli (including Bacteroides fragilis). Bacterial Septicemia caused by S. pneumoniae, S. agalactiae, S. aureus, Pseudomonas aeruginosa, E. coli, Klebsiella spp., Klebsiella pneumoniae, Proteus species (indole-positive and indole-negative), Clostridium spp. and anaerobic gram-positive cocci. Infections of the Skin and Skin Structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes, and P. aeruginosa. Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci. Cefobid has no activity against Chlamydia trachomatis. Therefore, when Cefobid is used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added. Urinary Tract Infections caused by Escherichia coli and Pseudomonas aeruginosa. Cefoperazone, a third-generation cephalosporin, interferes with cell wall synthesis by binding to the penicillin-binding proteins (PBPs), thus preventing cross-linking of nascent peptidoglycan. Cefoperazone is stable to penicillinases and has a high degree of stability to many beta-lactamases produced by gram-negative bacteria. When tested in vitro, cefoperazone has demonstrated synergistic interactions with aminoglycosides against gram-negative bacilli. As with all cephalosporins, hypersensitivity manifested by skin reactions or drug fever. Reversible neutropenia may occur with prolonged administration. Diarrhea or loose stools has been reported also.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial penicillin-binding protein 232 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6448021	Inhibitor 8146

Conditions

Condition	Modality	Highest Phase	Product
Respiratory tract infections 85 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Respiratory Tract Infections caused by S. pneumoniae, H. influenzae, S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes* (Group A beta-hemolytic streptococci), P. aeruginosa, Klebsiella pneumoniae, E. coli, Proteus mirabilis, and Enterobacter species. Launch Date 4.064256E11
Peritonitis and other intra-abdominal infections 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Peritonitis and Other Intra-abdominal Infections caused by E. coli, P. aeruginosa,* and anaerobic gram-negative bacilli (including Bacteroides fragilis). Launch Date 4.064256E11
Sepsis 71 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Bacterial Septicemia caused by S. pneumoniae, S. agalactiae, S. aureus, Pseudomonas aeruginosa, E. coli, Klebsiella spp., Klebsiella pneumoniae, Proteus species (indole-positive and indole-negative), Clostridium spp. and anaerobic gram-positive cocci. Launch Date 4.064256E11
Skin and skin structure infections 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Infections of the Skin and Skin Structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes,* and P. aeruginosa. Launch Date 4.064256E11
Pelvic inflammatory disease 12 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Pelvic Inflammatory Disease, Endometritis, and Other Infections of the Female Genital Tract caused by N. gonorrhoeae, S. epidermidis, S. agalactiae, E. coli, Clostridium spp., Bacteroides species (including Bacteroides fragilis), and anaerobic gram-positive cocci. Launch Date 4.064256E11
Urinary tract infections 202 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/050551s043lbl.pdf	Curative	Approved 8307	CEFOBID Approved Use Urinary Tract Infections caused by Escherichia coli and Pseudomonas aeruginosa. Launch Date 4.064256E11

C_max

Value	Dose	Co-administered	Analyte	Population
154.9 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
221.8 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
211.62 mg × h/L per 1.73 m² EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
421.63 mg × h/L per 1.73 m² EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1147.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg 3 times / day multiple, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
541.2 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	50 mg/kg 3 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
761.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.649 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.044 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3619425	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.063 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg 3 times / day multiple, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
0.185 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	50 mg/kg 3 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN
0.063 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6644441	100 mg/kg single, intravenous dose: 100 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	CEFOPERAZONE serum	Homo sapiens population: UNHEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 145 OAT1 584 OAT2 144 OAT3 625	P-gp 1491 OATP1B3 333 BCRP 545

Drug as perpetrator

Target	Modality	Activity
OAT2 146	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1330 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1890 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 210 uM]
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 2800 uM]

Drug as victim

Target	Modality	Activity
BCRP 545	substrate 3264 Sources: https://link.springer.com/article/10.1007/s11095-015-1641-2 Page: 5.0	yes
OATP1B3 333	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/21372390/	yes
P-gp 1491	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679430/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3493	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3493
ChemicalBook	CB4752040	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4752040
MolPort	MolPort-006-069-122	https://www.molport.com/shop/molecule-link/MolPort-006-069-122
Selleck Chemicals	cefoperazone-cefobid	http://www.selleckchem.com/products/cefoperazone-cefobid.html
ZINC	ZINC000003830432	http://zinc15.docking.org/substances/ZINC000003830432
eMolecules	3715751	https://www.emolecules.com/cgi-bin/more?vid=3715751

PubMed

Title	Date	PubMed
[Cefoperazone (Medocef*) in the modern therapy of severe bacterial infections].	2001	11881192
Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in vitro antibiotic release.	2001	11403236
[Bacterial flora in obstructed bile ducts].	2001 Apr	11387775
Prevalence and analysis of risk factors for infections caused by resistant Escherichia coli strains in Anhui, China.	2001 Aug	11545486
Antibiotic combinations in polymicrobic diabetic foot infections.	2001 Dec	12024991
Development of a new protocol for the isolation and quantification of Arcobacter species from poultry products.	2001 Dec 30	11789937
In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis.	2001 Jan	11085386
Randomized, double-blind, controlled study of cefoperazone-sulbactam plus cotrimoxazole versus ceftazidime plus cotrimoxazole for the treatment of severe melioidosis.	2001 Jul 1	11389491
[Characterization of cefoperazone resistance gene on plasmid pFC in E. coli HX88108].	2001 Mar	12733347
[Causative agents of bloodstream infections in children with neoplasm, in 5 hospitals of Santiago (1994-1998)].	2001 Nov	11836882
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
The penetration of cefoperazone and sulbactam into the lumbar intervertebral discs.	2001 Oct	11586148
Purification and characterization of a beta-lactamase from Haemophilus ducreyi in Escherichia coli.	2001 Oct	11570857
Calorimetric analysis of cephalosporins using an immobilized TEM-1 beta-lactamase on Ni2+ chelating sepharose fast flow.	2001 Sep 1	11520032
The importance of pets as reservoirs of resistant Enterococcus strains, with special reference to vancomycin.	2002 Aug	12241027
Klebsiella pneumoniae: epidemiology and analysis of risk factors for infections caused by resistant strains.	2002 Aug	12215282
[A control study on bacterial resistance and clinical features of lower respiratory tract infection with Pseudomonas aeruginosa in medical intensive care unit and general ward].	2002 Dec	12654234
[Molecular characteristics of beta-lactamase from Klebsiella pneumoniae].	2002 Feb 25	11953180
Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.	2002 Jul	12065749
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.	2002 Mar	12118443
Multiresistant Acinetobacter infections: a role for sulbactam combinations in overcoming an emerging worldwide problem.	2002 Mar	12010169
Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta-lactam antibiotics.	2002 Oct	12354209
Pseudomonas aeruginosa: resistance and therapy.	2002 Sep	12226802
Comparative study of antimicrobial resistance of Pseudomonas aeruginosa strains isolated from patients of Caracas and Asunción in a 4-year-period.	2002 Sep	12218262
[Efficacy and safety of cefoperazone/sulbactam in the treatment of children with mucoviscidosis during exacerbation of the bronchopulmonary process].	2003	15176099
[Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections].	2003	12914120
[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2002].	2003 Dec	15007873
[Current data on antibiotic resistance of the most important bovine mastitis pathogens in Switzerland].	2003 Dec	14725183
[Comparative analysis of the effectiveness and costs of azithromycin and cefoperazone treatment of patients during COPD exacerbation].	2003 Jan	12712826
Specific determination of unbound oxacillin in protein solution with cefoperazone by high-performance frontal analysis with chemiluminescence detection.	2003 Jan	12583007
[Activity of fourth generation cephalosporins against clinical isolates of Enterobacteriaceae].	2003 Jul-Sep	14756068
[Changes of antimicrobial resistance among nonfermenting gram-negative bacilli isolated from intensive care units from 1994 to 2001 in China].	2003 Mar 10	12820914
Square-wave voltammetric determination of cefoperazone in a bacterial culture, pharmaceutical drug, milk, and urine.	2003 Sep	12898110
Double-disk synergy test positivity in Stenotrophomonas maltophilia clinical strains.	2004	15114869
Pacemaker lead endocarditis caused by Achromobacter xylosoxidans.	2004 Apr	15082906
External decontamination of wild leeches with hypochloric acid.	2004 Aug 25	15329153
Isolation and characterisation of Arcobacter butzleri from meat.	2004 Feb 15	14967558
Derivatives of phosphate Schiff base transition metal complexes: synthesis, studies and biological activity.	2004 Jan	14670488
In vitro activities of beta-lactam antibiotics alone and in combination with sulbactam against Gram-negative bacteria.	2004 Jun	15194130
In vitro bactericidal activity of antimicrobial agents against enterohaemorrhagic Escherichia coli.	2004 Nov	15472004
Pharmacokinetics of quinacrine in the treatment of prion disease.	2004 Nov 29	15569390
[Survey of the utilization and adverse effects of antibacterial drugs in patients admitted for respiratory diseases].	2005 Feb	15699017
[Distribution and drug-resistance of 3 500 gram-negative bacteria in Guangzhou].	2005 Feb	15698988

Patents

Sample Use Guides

In Vivo Use Guide

The usual adult daily dose is 2 to 4 grams per day administered in equally divided doses every 12 hours. In severe infections or infections caused by less sensitive organisms, the total daily dose and/or frequency may be increased. Patients have been successfully treated with a total daily dosage of 6–12 grams divided into 2, 3 or 4 administrations ranging from 1.5 to 4 grams per dose. When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

Route of Administration: Other

In Vitro Use Guide

MIC90 of cefoperazone against S. marcescens, E. cloacae, ESBL-K. pneumoniae and A. baumannii were >128 mg/L.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 20:31:11 UTC 2022` Edited by `admin` on `Fri Dec 16 20:31:11 UTC 2022`
Record UNII	7U75I1278D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CEFOPERAZONE

Official Name

English

CEFOPERAZONE [MI]

Common Name

English

CEFOPERAZONE [VANDF]

Common Name

English

cefoperazone [INN]

Common Name

English

PERACEF

Brand Name

English

5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7-(((((4-ETHYL-2,3-DIOXO-1-PIPERAZINYL)CARBONYL)AMINO)(4-HYDROXYPHENYL)ACETYL)AMINO)-3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-8-OXO, (6R-(6.ALPHA.,7.BETA.(R*)))-

Common Name

English

Cefoperazone [WHO-DD]

Common Name

English

(6R,7R)-7-((R)-2-(4-ETHYL-2,3-DIOXO-1-PIPERAZINECARBOXAMIDO)-2-(P-HYDROXYPHENYL)ACETAMIDO-3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-8-OXO-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000011161