You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameCefoperazone
Accession NumberDB01329
Typesmall molecule
Groupsapproved
Description

Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It has been proposed especially against Pseudomonas infections.

Structure
Thumb
Synonyms
SynonymLanguageCode
CefoperazonoSpanishINN
CefoperazonumLatinINN
SaltsNot Available
Brand names
NameCompany
CefobidPfizer
CefobinePfizer
CefobisPfizer
CefoperazinPfizer
Brand mixturesNot Available
Categories
CAS number62893-19-0
WeightAverage: 645.667
Monoisotopic: 645.142400265
Chemical FormulaC25H27N9O8S2
InChI KeyGCFBRXLSHGKWDP-WTKTZPJXSA-N
InChI
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
IUPAC Name
(6R,7R)-7-(2-{[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino}-2-(4-hydroxyphenyl)acetamido)-3-{[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)C(NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=C(O)C=C1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentCephalosporins
Alternative parentsN-carbamoyl-alpha Amino Acids and Derivatives; Alpha Amino Acid Amides; Piperazine Carboxamides; Dioxopiperazines; Ureides; Phenols and Derivatives; Diazinanes; 1,3-Thiazines; N-substituted Carboxylic Acid Imides; Tertiary Carboxylic Acid Amides; Tetrazoles; Secondary Carboxylic Acid Amides; Hemiaminals; Tertiary Amines; Azetidines; Polyols; Polyamines; Enamines; Carboxylic Acids; Enolates; Aminals; Thioethers; Enols
Substituentsn-acyl-alpha amino acid or derivative; n-carbamoyl-alpha-amino acid or derivative; alpha-amino acid amide; alpha-amino acid or derivative; piperazine-1-carboxamide; dioxopiperazine; phenol derivative; ureide; carboxylic acid imide, n-substituted; benzene; piperazine; 1,4-diazinane; meta-thiazine; tetrazole; tertiary carboxylic acid amide; azole; hemiaminal; carboxamide group; polyol; azetidine; tertiary amine; secondary carboxylic acid amide; polyamine; enol; enamine; enolate; aminal; carboxylic acid derivative; thioether; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moeity or a derivative thereof.
Pharmacology
IndicationFor the treatment of bacterial infections caused by susceptible microorganisms.
PharmacodynamicsCefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis
Mechanism of actionLike all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingThe degree of reversible protein binding varies with the serum concentration from 93% at 25 mcg/mL to 90% at 250 mcg/mL and 82% at 500 mcg/mL. Cefotetan is 88% plasma protein bound.
Metabolism

No significant quanitity of metabolites have been identified in urine.

Route of eliminationCefoperazone is excreted mainly in the bile.
Half lifeThe mean serum half-life is approximately 2.0 hours, independent of the route of administration.
ClearanceNot Available
ToxicitySymptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.5526
Blood Brain Barrier - 0.9886
Caco-2 permeable - 0.7049
P-glycoprotein substrate Substrate 0.946
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.9759
Renal organic cation transporter Non-inhibitor 0.8099
CYP450 2C9 substrate Non-substrate 0.7919
CYP450 2D6 substrate Non-substrate 0.8101
CYP450 3A4 substrate Substrate 0.5899
CYP450 1A2 substrate Non-inhibitor 0.8022
CYP450 2C9 substrate Non-inhibitor 0.7458
CYP450 2D6 substrate Non-inhibitor 0.8502
CYP450 2C19 substrate Non-inhibitor 0.7271
CYP450 3A4 substrate Non-inhibitor 0.869
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6906
Ames test Non AMES toxic 0.6584
Carcinogenicity Non-carcinogens 0.9099
Biodegradation Not ready biodegradable 0.6674
Rat acute toxicity 2.4703 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8021
hERG inhibition (predictor II) Inhibitor 0.557
Pharmacoeconomics
Manufacturers
  • Pfizer laboratories div pfizer inc
  • Pfizer inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular
Powder, for solutionIntravenous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point188-190Saikawa, I., Takano, S., Yoshida, C., Takashima, 0..Momonoi, K., Kuroda, S., Komatsu, M., Yasuda, T.and Kodama, Y.; British Patent 1,508,071; April 19,1978; assigned to Toyama Chemical Co., Ltd. and U.S. Patent 4,110,327; August 29,1978; also assigned to Toyama Chemical Co., Ltd.
logP-0.74HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility2.86e-01 g/lALOGPS
logP-0.11ALOGPS
logP-0.9ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)3.38ChemAxon
pKa (strongest basic)-1.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count11ChemAxon
hydrogen donor count4ChemAxon
polar surface area220.26ChemAxon
rotatable bond count9ChemAxon
refractivity169.06ChemAxon
polarizability62.62ChemAxon
number of rings5ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Walter Cabri, “Process for the preparation of highly crystalline sodium cefoperazone.” U.S. Patent US20040030127, issued February 12, 2004.

US20040030127
General Reference
  1. Jones RN, Barry AL: Cefoperazone: a review of its antimicrobial spectrum, beta-lactamase stability, enzyme inhibition, and other in vitro characteristics. Rev Infect Dis. 1983 Mar-Apr;5 Suppl 1:S108-26. Pubmed
External Links
ResourceLink
KEGG CompoundC06883
PubChem Compound44185
PubChem Substance46504543
ChemSpider40204
ChEBI3493
ChEMBLCHEMBL507674
Therapeutic Targets DatabaseDAP000450
PharmGKBPA448849
WikipediaCefoperazone
ATC CodesJ01DD12
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(29 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmikacinIncreased risk of nephrotoxicity
GentamicinIncreased risk of nephrotoxicity
NetilmicinIncreased risk of nephrotoxicity
TobramycinIncreased risk of nephrotoxicity
Food InteractionsNot Available

Targets

1. Peptidoglycan synthase FtsI

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Peptidoglycan synthase FtsI P0AD68 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

2. Penicillin-binding protein 1B

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1B P02919 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

3. Penicillin-binding protein 2

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 2 P0AD65 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

4. Penicillin-binding protein 1A

Kind: protein

Organism: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A Q07806 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

5. Penicillin-binding protein 1B

Kind: protein

Organism: Pseudomonas aeruginosa

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1B Q9X6W0 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

6. D-alanyl-D-alanine carboxypeptidase DacC

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
D-alanyl-D-alanine carboxypeptidase DacC P08506 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

7. Penicillin-binding protein 1A

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A P02918 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

8. D-alanyl-D-alanine carboxypeptidase DacA

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
D-alanyl-D-alanine carboxypeptidase DacA P0AEB2 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

9. D-alanyl-D-alanine carboxypeptidase DacB

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
D-alanyl-D-alanine carboxypeptidase DacB P24228 Details

References:

  1. Matsubara N, Minami S, Matsuhashi M, Takaoka M, Mitsuhashi S: Affinity of cefoperazone for penicillin-binding proteins. Antimicrob Agents Chemother. 1980 Jul;18(1):195-9. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other/unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Liu LS, Zhang YY, Wang XP: [The reaction mechanism between cefoperazone and human serum albumin] Guang Pu Xue Yu Guang Pu Fen Xi. 2005 Sep;25(9):1490-2. Pubmed
  2. Gulian JM, Dalmasso C, Gonard V: Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin. Chemotherapy. 1990;36(2):91-7. Pubmed
  3. Leggett JE, Craig WA: Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli. Antimicrob Agents Chemother. 1989 Jan;33(1):35-40. Pubmed
  4. Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. Pubmed
  5. Nerli B, Farruggia B, Pico G: A comparative study of the binding characteristics of ceftriaxone, cefoperazone and cefsulodin to human serum albumin. Biochem Mol Biol Int. 1996 Nov;40(4):823-31. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. Pubmed

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

3. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

4. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. Eur J Pharmacol. 2003 Mar 28;465(1-2):1-7. Pubmed
  2. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. Pubmed
  3. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. Pubmed

Comments
comments powered by Disqus
Drug created on June 30, 2007 11:50 / Updated on April 03, 2014 09:51