Identification
NameCeftizoxime
Accession NumberDB01332
TypeSmall Molecule
GroupsApproved
Description

A semisynthetic cephalosporin antibiotic which can be administered intravenously or by suppository. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders. [PubChem]

Structure
Thumb
Synonyms
7-[2-(2-Amino-thiazol-4-yl)-2-methoxyimino-acetylamino]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Ceftizoxima
Ceftizoxime
Ceftizoximum
Syn-7-(2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido)-3-cephem-4-carboxylic acid
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Ceftizoxime sodium26337D5X88 68401-82-1ADLFUPFRVXCDMO-LIGXYSTNSA-MDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CefizoxPowder, for solution1 gIntramuscular; IntravenousGlaxosmithkline Inc1988-12-312005-10-19Canada
CefizoxPowder, for solution2 gIntramuscular; IntravenousGlaxosmithkline Inc1988-12-312005-10-19Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CEFIZOXNot Available
EpocelinChoseido Pharmaceutical
Brand mixturesNot Available
Categories
UNIIC43C467DPE
CAS number68401-81-0
WeightAverage: 383.403
Monoisotopic: 383.035809931
Chemical FormulaC13H13N5O5S2
InChI KeyNNULBSISHYWZJU-LLKWHZGFSA-N
InChI
InChI=1S/C13H13N5O5S2/c1-23-17-7(5-4-25-13(14)15-5)9(19)16-8-10(20)18-6(12(21)22)2-3-24-11(8)18/h2,4,8,11H,3H2,1H3,(H2,14,15)(H,16,19)(H,21,22)/b17-7-/t8-,11-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC=C(N1C(=O)[[email protected]]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O
Pharmacology
Indication

For the treatment of infections due to susceptible strains of microorganisms.

Structured Indications Not Available
Pharmacodynamics

Ceftizoxime is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders.

Mechanism of action

Ceftizoxime is an aminothiazolyl cephalosporin with an extended spectrum of activity against many gram-negative, nosocomially acquired pathogens. It has excellent beta-lactamase stability, with good in vitro activity against Haemophilus influenzae, Neisseria gonorrhoeae and Klebsiella pneumoniae. Ceftizoxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that ceftizoxime interferes with an autolysin inhibitor.

TargetKindPharmacological actionActionsOrganismUniProt ID
MecA PBP2' (penicillin binding protein 2')Proteinyes
inhibitor
Staphylococcus aureusQ53707 details
Penicillin-binding protein 1AProteinyes
inhibitor
Escherichia coli (strain K12)P02918 details
Penicillin-binding protein 1BProteinyes
inhibitor
Escherichia coli (strain K12)P02919 details
Peptidoglycan synthase FtsIProteinyes
inhibitor
Escherichia coli (strain K12)P0AD68 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding

30% protein bound

Metabolism

Ceftizoxime is not metabolized, and is excreted virtually unchanged by the kidneys in 24 hours.

Route of elimination

Ceftizoxime is not metabolized, and is excreted virtually unchanged by the kidneys in 24 hours.

Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolCeftizoxime may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Ceftizoxime.Investigational
DicoumarolCeftizoxime may increase the anticoagulant activities of Dicoumarol.Approved
Ethyl biscoumacetateCeftizoxime may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCeftizoxime may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCeftizoxime may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonCeftizoxime may increase the anticoagulant activities of Phenprocoumon.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Ceftizoxime.Approved
ProbenecidThe serum concentration of Ceftizoxime can be increased when it is combined with Probenecid.Approved
WarfarinCeftizoxime may increase the anticoagulant activities of Warfarin.Approved
Food InteractionsNot Available
References
Synthesis Reference

Norio Ohnishi, Rinta Ibuki, "Method for preparing stable crystals of salt of Ceftizoxime." U.S. Patent US4390694, issued October, 1981.

US4390694
General ReferencesNot Available
External Links
ATC CodesJ01DD07 — Ceftizoxime
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
4CompletedPreventionCaesarean1
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular; Intravenous1 g
Powder, for solutionIntramuscular; Intravenous2 g
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1321580 No1993-08-242010-08-24Canada
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)277Takaya, T., Masugi, T., Takasugi, H. and Kochi, H.;U.S. Patent 4,166,115; assigned to Fuji- sawa Pharmaceutical & ., Ltd.
Predicted Properties
PropertyValueSource
Water Solubility0.229 mg/mLALOGPS
logP0.4ALOGPS
logP-0.85ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.13ChemAxon
pKa (Strongest Basic)4.16ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area147.21 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity89.9 m3·mol-1ChemAxon
Polarizability35.38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7379
Blood Brain Barrier-0.9823
Caco-2 permeable-0.7273
P-glycoprotein substrateSubstrate0.5819
P-glycoprotein inhibitor INon-inhibitor0.9194
P-glycoprotein inhibitor IINon-inhibitor0.8007
Renal organic cation transporterNon-inhibitor0.8794
CYP450 2C9 substrateNon-substrate0.804
CYP450 2D6 substrateNon-substrate0.8281
CYP450 3A4 substrateNon-substrate0.5393
CYP450 1A2 substrateNon-inhibitor0.749
CYP450 2C9 inhibitorNon-inhibitor0.8202
CYP450 2D6 inhibitorNon-inhibitor0.9005
CYP450 2C19 inhibitorNon-inhibitor0.7881
CYP450 3A4 inhibitorNon-inhibitor0.7951
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9449
Ames testNon AMES toxic0.7835
CarcinogenicityNon-carcinogens0.8563
BiodegradationNot ready biodegradable0.9906
Rat acute toxicity1.8332 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9903
hERG inhibition (predictor II)Non-inhibitor0.918
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 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 moiety or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentCephalosporins
Alternative ParentsN-acyl-alpha amino acids and derivatives / 2,4-disubstituted thiazoles / 1,3-thiazines / 2-amino-1,3-thiazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Amino acids / Azetidines / Thiohemiaminal derivatives
SubstituentsCephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / 2,4-disubstituted 1,3-thiazole / Meta-thiazine / 1,3-thiazol-2-amine / Azole / Heteroaromatic compound / Tertiary carboxylic acid amide / Thiazole
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorscephalosporin (CHEBI:553473 )

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
mecA
Uniprot ID:
Q53707
Uniprot Name:
MecA PBP2' (penicillin binding protein 2')
Molecular Weight:
76265.485 Da
References
  1. Leski TA, Tomasz A: Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. J Bacteriol. 2005 Mar;187(5):1815-24. [PubMed:15716453 ]
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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
Gene Name:
mrcA
Uniprot ID:
P02918
Uniprot Name:
Penicillin-binding protein 1A
Molecular Weight:
93635.545 Da
References
  1. Shigi Y, Kojo H, Wakasugi M, Nishida M: Differences between ceftizoxime and its stereoisomer in antibacterial activity and affinity for penicillin-binding proteins. Antimicrob Agents Chemother. 1981 Mar;19(3):393-6. [PubMed:7018389 ]
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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
Gene Name:
mrcB
Uniprot ID:
P02919
Uniprot Name:
Penicillin-binding protein 1B
Molecular Weight:
94291.875 Da
References
  1. Shigi Y, Kojo H, Wakasugi M, Nishida M: Differences between ceftizoxime and its stereoisomer in antibacterial activity and affinity for penicillin-binding proteins. Antimicrob Agents Chemother. 1981 Mar;19(3):393-6. [PubMed:7018389 ]
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 from the lipid-linked precursors (PubMed:7030331). Required for localization of FtsN (PubMed:9282742).
Gene Name:
ftsI
Uniprot ID:
P0AD68
Uniprot Name:
Peptidoglycan synthase FtsI
Molecular Weight:
63876.925 Da
References
  1. Shigi Y, Kojo H, Wakasugi M, Nishida M: Differences between ceftizoxime and its stereoisomer in antibacterial activity and affinity for penicillin-binding proteins. Antimicrob Agents Chemother. 1981 Mar;19(3):393-6. [PubMed:7018389 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Uniprot Name:
Solute carrier family 15 member 1
Molecular Weight:
78805.265 Da
References
  1. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [PubMed:15618677 ]
Drug created on June 30, 2007 12:05 / Updated on September 01, 2017 10:38