Cefoperazone

Identification

Summary

Cefoperazone is a broad-spectrum cephalosporin antibiotic used for the treatment of bacterial infections in various locations, including the respiratory tract, abdomen, skin, and female genital tracts.

Generic Name
Cefoperazone
DrugBank Accession Number
DB01329
Background

Cefoperazone is a semisynthetic broad-spectrum cephalosporin proposed to be effective against Pseudomonas infections. It is a third-generation antiobiotic agent and it is used in the treatment of various bacterial infections caused by susceptible organisms in the body, including respiratory tract infections, peritonitis, skin infections, endometritis, and bacterial septicemia. While its clinical use has been discontinued in the U.S., cefoperazone is available in several European countries most commonly under the product name, Sulperazon.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 645.67
Monoisotopic: 645.142401213
Chemical Formula
C25H27N9O8S2
Synonyms
  • (6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxo-1-piperazinylcarboxamido)-2-(4-hydroxyphenyl)acetamido)-3-((1-methyl-1H-tetrazol-5-yl)thiomethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-2-carbonsaeure
  • (6R,7R)-7-[[2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • Cefoperazone
  • Cefoperazono
  • Cefoperazonum

Pharmacology

Indication

Indicated for the treatment of following infections caused by susceptible bacteria:Label

1) 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.

2) Peritonitis and other intra-abdominal infections caused by E. coli, P. aeruginosa, and anaerobic gram-negative bacilli (including Bacteroides fragilis).

3) 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.

4) Infections of the skin and skin structures caused by S. aureus (penicillinase and non-penicillinase producing strains), S. pyogenes, and P. aeruginosa.

5) 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.

6) Urinary tract infections caused by Escherichia coli and Pseudomonas aeruginosa.

7) Enterococcal Infections. Although cefoperazone has been shown to be clinically effective in the treatment of infections caused by enterococci in cases of peritonitis and other intra-abdominal infections, infections of the skin and skin structures, pelvic inflammatory disease, endometritis and other infections of the female genital tract, and urinary tract infections, the majority of clinical isolates of enterococci tested are not susceptible to cefoperazone but fall just at or in the intermediate zone of susceptibility, and are moderately resistant to cefoperazone. However, in vitro susceptibility testing may not correlate directly with in vivo results. Despite this, cefoperazone therapy has resulted in clinical cures of enterococcal infections, chiefly in polymicrobial infections. Cefoperazone should be used in enterococcal infections with care and at doses that achieve satisfactory serum levels of cefoperazone.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatBacterial infectionsCombination Product in combination with: Sulbactam (DB09324)••••••••••••
Treatment ofBloodstream infections••••••••••••
Treatment ofBone and joint infections••••••••••••
Treatment ofIntra-abdominal infections••••••••••••
Treatment ofLower respiratory tract infection (lrti)••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis

Mechanism of action

Like 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.

TargetActionsOrganism
APeptidoglycan synthase FtsI
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1A
inhibitor
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
APenicillin-binding protein 1B
inhibitor
Pseudomonas aeruginosa
AD-alanyl-D-alanine carboxypeptidase DacC
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
AD-alanyl-D-alanine carboxypeptidase DacA
inhibitor
Escherichia coli (strain K12)
AD-alanyl-D-alanine carboxypeptidase DacB
inhibitor
Escherichia coli (strain K12)
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

The 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 elimination

Cefoperazone is excreted mainly in the bile.

Half-life

The mean serum half-life is approximately 2.0 hours, independent of the route of administration.

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirCefoperazone may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Cefoperazone.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Cefoperazone.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Cefoperazone is combined with Aceclofenac.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Cefoperazone is combined with Acemetacin.
Food Interactions
  • Avoid alcohol. Ingesting alcohol with cefoperazone may precipitate a disulfuram like reaction including symptoms such as flushing, tachycardia, sweating, and headache.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Cefoperazone sodium5FQG9774WD62893-20-3NCFTXMQPRQZFMZ-WERGMSTESA-M
International/Other Brands
Cefobine (Pfizer) / Cefobis (Pfizer) / Cefoperazin (Pfizer)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CefobidPowder, for solution1 g/1IntravenousRoerig1982-11-182003-03-01US flag
CefobidPowder, for solution10 g/1IntravenousRoerig1982-11-182003-03-01US flag
CefobidPowder, for solution2 g/1IntravenousRoerig1982-11-182003-03-01US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BAXCEFCefoperazone (0.5 g) + Sulbactam (0.5 g)Injection, powder, for solutionIntramuscular; IntravenousSolas Langgeng Sejahtera2016-01-142026-01-14Indonesia flag
Cebactam Injection 1gCefoperazone sodium (500 mg) + Sulbactam sodium (500 mg)Injection, powder, for solutionIntramuscular; IntravenousHEALOL PHARMACEUTICALS SDN. BHD.2020-09-082022-03-03Malaysia flag
CEFOPERAZONE SODIUM - SULBACTAM SODIUMCefoperazone (500 mg) + Sulbactam (500 mg)Injection, powder, for solutionIntramuscular; IntravenousBernofarm2016-07-112025-05-08Indonesia flag
CEFOPERAZONE SODIUM - SULBACTAM SODIUMCefoperazone (500 mg) + Sulbactam (500 mg)Injection, powder, for solutionIntramuscular; IntravenousNatura Laboratoria Prima2018-12-312025-05-08Indonesia flag
CEFOPERAZONE SODIUM - SULBACTAM SODIUMCefoperazone sodium (500 mg) + Sulbactam sodium (500 mg)Injection, powder, for solutionIntramuscular; IntravenousInfion2015-10-052025-05-08Indonesia flag

Categories

ATC Codes
J01DD12 — Cefoperazone
Drug Categories
Classification
Not classified
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
7U75I1278D
CAS number
62893-19-0
InChI Key
GCFBRXLSHGKWDP-XCGNWRKASA-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-[(2R)-2-[(4-ethyl-2,3-dioxopiperazine-1-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@@]2([H])NC(=O)[C@H](NC(=O)N1CCN(CC)C(=O)C1=O)C1=CC=C(O)C=C1)C(O)=O

References

Synthesis Reference

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

US20040030127
General References
  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. [Article]
  2. TITCK Product Information: Cefobid (cefoperazone sodium) for intramuscular/intravenous injection [Link]
Human Metabolome Database
HMDB0015424
KEGG Compound
C06883
PubChem Compound
44185
PubChem Substance
46504543
ChemSpider
40206
BindingDB
50390999
RxNav
2184
ChEBI
3493
ChEMBL
CHEMBL507674
ZINC
ZINC000003830432
Therapeutic Targets Database
DAP000450
PharmGKB
PA448849
Wikipedia
Cefoperazone
FDA label
Download (174 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4Active Not RecruitingOtherInfectious Diseases1somestatusstop reasonjust information to hide
4CompletedTreatmentAnti-drug antibody development / Cholangitis, Secondary Biliary / Compliance, Treatment1somestatusstop reasonjust information to hide
4CompletedTreatmentInfection1somestatusstop reasonjust information to hide
4Unknown StatusTreatmentPancreatitis,Acute Necrotizing1somestatusstop reasonjust information to hide
2SuspendedTreatmentRespiratory Tract Infections (RTI) / Urinary Tract Infection1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
Dosage Forms
FormRouteStrength
InjectionIntramuscular; Intravenous1 g
Injection, powder, for solutionIntramuscular
Injection, powder, for solutionIntravenous
Powder, for solutionIntravenous1 g/1
Powder, for solutionIntravenous10 g/1
Powder, for solutionIntravenous2 g/1
Injection, powder, for solutionIntramuscular; Intravenous
Injection, powder, for solutionIntramuscular; Intravenous1 gr
InjectionParenteral1 g
Injection, powder, for solutionParenteral
InjectionParenteral2 g
Powder, for solutionIntravenous
Injection, powder, for solution1.088 g
Injection, powder, for solution1.12 g
PowderIntravenous
InjectionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous
Injection, powder, for solutionIntramuscular; Intravenous1 g
Injection, powder, for solutionIntramuscular; Intravenous500 mg
InjectionIntramuscular; Intravenous
Injection, powder, for solution1 G
Injection, powder, for solution2 GM
Injection, powder, for solution
Injection, powder, for solutionIntramuscular; Intravenous
Injection, solutionIntramuscular
InjectionIntramuscular
Powder
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)188-190Saikawa, 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 Solubility0.286 mg/mLALOGPS
logP-0.11ALOGPS
logP-0.9Chemaxon
logS-3.4ALOGPS
pKa (Strongest Acidic)3.19Chemaxon
pKa (Strongest Basic)-1.7Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count11Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area220.26 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity169.06 m3·mol-1Chemaxon
Polarizability60.97 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.5526
Blood Brain Barrier-0.9886
Caco-2 permeable-0.7049
P-glycoprotein substrateSubstrate0.946
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.9759
Renal organic cation transporterNon-inhibitor0.8099
CYP450 2C9 substrateNon-substrate0.7919
CYP450 2D6 substrateNon-substrate0.8101
CYP450 3A4 substrateSubstrate0.5899
CYP450 1A2 substrateNon-inhibitor0.8022
CYP450 2C9 inhibitorNon-inhibitor0.7458
CYP450 2D6 inhibitorNon-inhibitor0.8502
CYP450 2C19 inhibitorNon-inhibitor0.7271
CYP450 3A4 inhibitorNon-inhibitor0.869
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6906
Ames testNon AMES toxic0.6584
CarcinogenicityNon-carcinogens0.9099
BiodegradationNot ready biodegradable0.6674
Rat acute toxicity2.4703 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8021
hERG inhibition (predictor II)Inhibitor0.557
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 MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0007-0729208000-8924c6a705686e8a45e3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0709212000-55e1f472278a426eb4c3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-002f-1913242000-a60ff30cf205c8d85bba
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-3900001000-c646a12df07bdc4a620a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-006x-4900021000-ce78b3b0944f9bb65d82
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0839284000-5c8f84bd6039638c9655
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-235.7793853
predicted
DarkChem Lite v0.1.0
[M+H]+234.7044853
predicted
DarkChem Lite v0.1.0
[M+Na]+234.7592853
predicted
DarkChem Lite v0.1.0

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
Specific Function
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan fr...
Gene Name
ftsI
Uniprot ID
P0AD68
Uniprot Name
Peptidoglycan synthase FtsI
Molecular Weight
63876.925 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
94291.875 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name
mrdA
Uniprot ID
P0AD65
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
70856.1 Da
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. [Article]
Kind
Protein
Organism
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcA
Uniprot ID
Q07806
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
91198.715 Da
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. [Article]
Kind
Protein
Organism
Pseudomonas aeruginosa
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
ponB
Uniprot ID
Q9X6W0
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
85486.615 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Gene Name
dacC
Uniprot ID
P08506
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacC
Molecular Weight
43608.595 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
93635.545 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Gene Name
dacA
Uniprot ID
P0AEB2
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacA
Molecular Weight
44443.62 Da
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. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction.
Gene Name
dacB
Uniprot ID
P24228
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacB
Molecular Weight
51797.85 Da
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Other/unknown
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
Antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
Alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
Organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
Specific Function
Organic anion transmembrane transporter activity
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively (PubMed:11327718, PubMed:25904762). Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates (PubMed:11327718, PubMed:18216183, PubMed:26377792, PubMed:28945155). Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways (PubMed:18216183, PubMed:26377792). Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood (PubMed:21446918). Involved in renal secretion and possible reabsorption of creatinine (PubMed:25904762, PubMed:28945155). Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate (PubMed:11327718, PubMed:26377792). Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified (PubMed:26377792)
Specific Function
Alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
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. [Article]
  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. [Article]
  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. [Article]

Drug created at June 30, 2007 17:50 / Updated at June 02, 2024 21:58