Identification

Name
Ceftizoxime
Accession Number
DB01332
Type
Small Molecule
Groups
Approved, Investigational
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
Product Ingredients
IngredientUNIICASInChI Key
Ceftizoxime sodium26337D5X8868401-82-1ADLFUPFRVXCDMO-LIGXYSTNSA-M
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
International/Other Brands
CEFIZOX / Epocelin (Choseido Pharmaceutical)
Categories
UNII
C43C467DPE
CAS number
68401-81-0
Weight
Average: 383.403
Monoisotopic: 383.035809931
Chemical Formula
C13H13N5O5S2
InChI Key
NNULBSISHYWZJU-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][C@]12SCC=C(N1C(=O)[C@H]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.

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.

TargetActionsOrganism
AMecA PBP2' (penicillin binding protein 2')
inhibitor
Staphylococcus aureus
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
APeptidoglycan synthase FtsI
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution
Not 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 life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCeftizoxime may increase the anticoagulant activities of Acenocoumarol.Approved, Investigational
AmikacinCeftizoxime may increase the nephrotoxic activities of Amikacin.Approved, Investigational, Vet Approved
ApramycinCeftizoxime may increase the nephrotoxic activities of Apramycin.Experimental, Vet Approved
ArbekacinCeftizoxime may increase the nephrotoxic activities of Arbekacin.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ceftizoxime.Investigational
BekanamycinCeftizoxime may increase the nephrotoxic activities of Bekanamycin.Experimental
ClorindioneCeftizoxime may increase the anticoagulant activities of Clorindione.Experimental
DibekacinCeftizoxime may increase the nephrotoxic activities of Dibekacin.Experimental
DicoumarolCeftizoxime may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinCeftizoxime may increase the nephrotoxic activities of Dihydrostreptomycin.Investigational, Vet Approved
DiphenadioneCeftizoxime may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCeftizoxime may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCeftizoxime may increase the anticoagulant activities of Fluindione.Approved, Investigational
FramycetinCeftizoxime may increase the nephrotoxic activities of Framycetin.Approved
GeneticinCeftizoxime may increase the nephrotoxic activities of Geneticin.Experimental
GentamicinCeftizoxime may increase the nephrotoxic activities of Gentamicin.Approved, Vet Approved
GENTAMICIN C1ACeftizoxime may increase the nephrotoxic activities of GENTAMICIN C1A.Experimental
Hygromycin BCeftizoxime may increase the nephrotoxic activities of Hygromycin B.Vet Approved
IsepamicinCeftizoxime may increase the nephrotoxic activities of Isepamicin.Experimental
KanamycinCeftizoxime may increase the nephrotoxic activities of Kanamycin.Approved, Investigational, Vet Approved
MicronomicinCeftizoxime may increase the nephrotoxic activities of Micronomicin.Experimental
NeamineCeftizoxime may increase the nephrotoxic activities of Neamine.Experimental
NeomycinCeftizoxime may increase the nephrotoxic activities of Neomycin.Approved, Vet Approved
NetilmicinCeftizoxime may increase the nephrotoxic activities of Netilmicin.Approved, Investigational
ParomomycinCeftizoxime may increase the nephrotoxic activities of Paromomycin.Approved, Investigational
PhenindioneCeftizoxime may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCeftizoxime may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Ceftizoxime.Approved
PlazomicinCeftizoxime may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
ProbenecidThe serum concentration of Ceftizoxime can be increased when it is combined with Probenecid.Approved, Investigational
PuromycinCeftizoxime may increase the nephrotoxic activities of Puromycin.Experimental
RibostamycinCeftizoxime may increase the nephrotoxic activities of Ribostamycin.Approved, Investigational
SisomicinCeftizoxime may increase the nephrotoxic activities of Sisomicin.Investigational
StreptomycinCeftizoxime may increase the nephrotoxic activities of Streptomycin.Approved, Vet Approved
TioclomarolCeftizoxime may increase the anticoagulant activities of Tioclomarol.Experimental
TobramycinCeftizoxime may increase the nephrotoxic activities of Tobramycin.Approved, Investigational
WarfarinCeftizoxime may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0015427
KEGG Compound
C06890
PubChem Compound
6533629
PubChem Substance
46505647
ChemSpider
5018818
BindingDB
237182
ChEBI
553473
ChEMBL
CHEMBL528
Therapeutic Targets Database
DAP000453
PharmGKB
PA164748758
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ceftizoxime
ATC Codes
J01DD07 — Ceftizoxime

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
4CompletedPreventionCaesarean1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
  • GlaxoSmithKline Inc.
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular; Intravenous1 g
Powder, for solutionIntramuscular; Intravenous2 g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1321580No1993-08-242010-08-24Canada

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporins
Alternative Parents
N-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
show 9 more
Substituents
Cephalosporin / 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
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (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 str...
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 str...
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 fr...
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Substrate profile was investigated during in vitro studies using HEK293 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [PubMed:19953504]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate and inhibitor profile were studied in vitro using human OAT3 expressed on HEK293 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [PubMed:19953504]

Drug created on June 30, 2007 12:05 / Updated on July 02, 2018 20:42