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Identification
NameCeftibuten
Accession NumberDB01415
TypeSmall Molecule
GroupsApproved
DescriptionCeftibuten is a third-generation cephalosporin antibiotic. It is an orally-administered agent. Cefalexin is used to treat acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis.
Structure
Thumb
Synonyms
(+)-(6R,7R)-7-((Z)-2-(2-amino-4-Thiazolyl)-4-carboxycrotonamido)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid
Ceftibutene
Ceftibuteno
Ceftibutenum
cis-Ceftibuten
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CedaxCapsule400 mg/1OralPernix Therapeutics, LLC1995-12-20Not applicableUs
CedaxSuspension180 mg/5mLOralPernix Therapeutics, LLC2010-10-20Not applicableUs
CedaxCapsule400 mg/1OralSciele Pharma, Inc.1995-12-20Not applicableUs
CedaxSuspension18 mg/mLOralSciele Pharma, Inc.1995-12-20Not applicableUs
CeftibutenSuspension180 mg/5mLOralMacoven Pharmaceuticals2013-10-01Not applicableUs
CeftibutenCapsule400 mg/1OralMacoven Pharmaceuticals2013-10-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ceftibuten dihydrate
ThumbNot applicableDBSALT001212
Categories
UNIIIW71N46B4Y
CAS number97519-39-6
WeightAverage: 410.425
Monoisotopic: 410.03547558
Chemical FormulaC15H14N4O6S2
InChI KeyUNJFKXSSGBWRBZ-BJCIPQKHSA-N
InChI
InChI=1S/C15H14N4O6S2/c16-15-17-7(5-27-15)6(1-2-9(20)21)11(22)18-10-12(23)19-8(14(24)25)3-4-26-13(10)19/h1,3,5,10,13H,2,4H2,(H2,16,17)(H,18,22)(H,20,21)(H,24,25)/b6-1-/t10-,13-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-4-carboxybut-2-enamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC=C(N1C(=O)[[email protected]]2NC(=O)C(=C/CC(O)=O)\C1=CSC(N)=N1)C(O)=O
Pharmacology
IndicationUsed to treat acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis.
Structured Indications
PharmacodynamicsCeftibuten is a third-generation cephalosporin antibiotic.
Mechanism of actionCeftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis.
TargetKindPharmacological actionActionsOrganismUniProt ID
Peptidoglycan synthase FtsIProteinyes
inhibitor
Escherichia coli (strain K12)P0AD68 details
Penicillin-binding protein 1AProteinyes
inhibitor
Escherichia coli (strain K12)P02918 details
Penicillin-binding protein 1BProteinyes
inhibitor
Escherichia coli (strain K12)P02919 details
Penicillin-binding protein 2Proteinyes
inhibitor
Escherichia coli (strain K12)P0AD65 details
Related Articles
AbsorptionRapidly absorbed following oral administration.
Volume of distribution
  • 0.21 L/kg [adult subjects]
  • 0.5 L/kg [fasting pediatric patients]
Protein bindingCeftibuten is 65% bound to plasma proteins. The protein binding is independent of plasma ceftibuten concentration.
Metabolism

A study with radiolabeled ceftibuten administered to 6 healthy adult male volunteers demonstrated that cis-ceftibuten is the predominant component in both plasma and urine. About 10% of ceftibuten is converted to the trans-isomer is approximately 1/8 as antimicrobially potent as the cis-isomer.

Route of eliminationCeftibuten is excreted in the urine; 95% of the administered radioactivity was recovered either in urine or feces.
Half lifeNot Available
ClearanceNot Available
ToxicityOverdosage of cephalosporins can cause cerebral irritation leading to convulsions.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Ceftibuten.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Ceftibuten.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesJ01DD14
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5755
Blood Brain Barrier-0.9679
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.5424
P-glycoprotein inhibitor INon-inhibitor0.9274
P-glycoprotein inhibitor IINon-inhibitor0.9586
Renal organic cation transporterNon-inhibitor0.929
CYP450 2C9 substrateNon-substrate0.8531
CYP450 2D6 substrateNon-substrate0.8293
CYP450 3A4 substrateNon-substrate0.6007
CYP450 1A2 substrateNon-inhibitor0.8787
CYP450 2C9 inhibitorNon-inhibitor0.8817
CYP450 2D6 inhibitorNon-inhibitor0.9191
CYP450 2C19 inhibitorNon-inhibitor0.8833
CYP450 3A4 inhibitorNon-inhibitor0.9625
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9387
Ames testNon AMES toxic0.7274
CarcinogenicityNon-carcinogens0.8961
BiodegradationNot ready biodegradable0.9688
Rat acute toxicity1.6446 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9848
hERG inhibition (predictor II)Non-inhibitor0.9305
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SuspensionOral18 mg/mL
CapsuleOral400 mg/1
SuspensionOral180 mg/5mL
Prices
Unit descriptionCostUnit
Cedax 400 mg capsule16.13USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4634697 No1992-10-012009-10-01Us
US5599557 No1994-02-042014-02-04Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0705 mg/mLALOGPS
logP0.31ALOGPS
logP-1.4ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)2.99ChemAxon
pKa (Strongest Basic)4.69ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area162.92 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity97.02 m3·mol-1ChemAxon
Polarizability38.5 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
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 Parents
Substituents
  • Cephalosporin
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid or derivatives
  • 2,4-disubstituted 1,3-thiazole
  • Primary aromatic amine
  • N-acyl-amine
  • Dicarboxylic acid or derivatives
  • Meta-thiazine
  • Heteroaromatic compound
  • Thiazole
  • Tertiary carboxylic acid amide
  • Azole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Hemithioaminal
  • Thioether
  • Enamine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

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
Molecular Weight:
63876.925 Da
References
  1. Wise R, Andrews JM, Ashby JP, Thornber D: Ceftibuten--in-vitro activity against respiratory pathogens, beta-lactamase stability and mechanism of action. J Antimicrob Chemother. 1990 Aug;26(2):209-13. [PubMed:2120175 ]
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
Molecular Weight:
93635.545 Da
References
  1. Wise R, Andrews JM, Ashby JP, Thornber D: Ceftibuten--in-vitro activity against respiratory pathogens, beta-lactamase stability and mechanism of action. J Antimicrob Chemother. 1990 Aug;26(2):209-13. [PubMed:2120175 ]
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
Molecular Weight:
94291.875 Da
References
  1. Wise R, Andrews JM, Ashby JP, Thornber D: Ceftibuten--in-vitro activity against respiratory pathogens, beta-lactamase stability and mechanism of action. J Antimicrob Chemother. 1990 Aug;26(2):209-13. [PubMed:2120175 ]
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
Molecular Weight:
70856.1 Da
References
  1. Wise R, Andrews JM, Ashby JP, Thornber D: Ceftibuten--in-vitro activity against respiratory pathogens, beta-lactamase stability and mechanism of action. J Antimicrob Chemother. 1990 Aug;26(2):209-13. [PubMed:2120175 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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
Molecular Weight:
78805.265 Da
References
  1. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. [PubMed:9092716 ]
  2. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297 ]
  3. Saito H, Okuda M, Terada T, Sasaki S, Inui K: Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther. 1995 Dec;275(3):1631-7. [PubMed:8531138 ]
  4. Terada T, Saito H, Mukai M, Inui K: Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J Pharmacol Exp Ther. 1997 Jun;281(3):1415-21. [PubMed:9190878 ]
  5. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833 ]
  6. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [PubMed:15618677 ]
  7. Menon RM, Barr WH: Transporters involved in apical and basolateral uptake of ceftibuten into Caco-2 cells. Biopharm Drug Dispos. 2002 Nov;23(8):317-26. [PubMed:12415572 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. [PubMed:9092716 ]
  2. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833 ]
  3. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297 ]
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Drug created on July 23, 2007 07:06 / Updated on August 17, 2016 12:23