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targets (4) transporters (2)
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Identification
Name Ceftibuten
Accession Number DB01415
Type small molecule
Groups approved
Description

Ceftibuten 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.
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Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Cedax
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Cephalosporins
CAS number 97519-39-6
Weight Average: 410.425
Monoisotopic: 410.035475580
Chemical Formula C15H14N4O6S2
InChI Key InChIKey=UNJFKXSSGBWRBZ-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
Plain Text
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)[C@H]2NC(=O)C(=C/CC(O)=O)\C1=CSC(N)=N1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Thiazoles
  • Cephalosporins
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Beta Lactams
  • Enamines
  • Isoprenes
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Cephalosporins
  • Lactams
  • Imines
  • Azetidines
Pharmacology
Indication Used to treat acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis.
Pharmacodynamics Ceftibuten is a third-generation cephalosporin antibiotic.
Mechanism of action Ceftibuten exerts its bactericidal action by binding to essential target proteins of the bacterial cell wall. This binding leads to inhibition of cell-wall synthesis.
Absorption Rapidly absorbed following oral administration.
Volume of distribution
  • 0.21 L/kg [adult subjects]
  • 0.5 L/kg [fasting pediatric patients]
Protein binding Ceftibuten 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 elimination Ceftibuten is excreted in the urine; 95% of the administered radioactivity was recovered either in urine or feces.
Half life Not Available
Clearance Not Available
Toxicity Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pernix therapeutics llc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Suspension Oral
Prices
Unit description Cost Unit
Cedax 400 mg capsule 16.13 USD capsule
Patents
Country Patent Number Approved Expires
United States 5599557 1994-02-04 2014-02-04
United States 4634697 1992-10-01 2009-10-01
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 7.05e-02 g/l ALOGPS
logP 0.31 ALOGPS
logP -1.53 ChemAxon Molconvert
logS -3.77 ALOGPS
pKa 3.68 ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 162.92 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 97.02 ChemAxon Molconvert
polarizability 38.50 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00922 Link_out
KEGG Compound C08117 Link_out
PubChem Compound 5282242 Link_out
PubChem Substance 46507324 Link_out
ChemSpider 4445418 Link_out
ChEBI 3510 Link_out
ChEMBL 3510 Link_out
Therapeutic Targets Database DAP000456 Link_out
PharmGKB PA448862 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/ceftibuten.htm Link_out
Drugs.com http://www.drugs.com/cdi/ceftibuten.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ced1075.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Ceftibuten Link_out
ATC Codes
  • J01DD14
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Peptidoglycan synthetase ftsI

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates

Organism class: bacterial
UniProt ID: P0AD68 Link_out
Gene: ftsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

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)

Organism class: bacterial
UniProt ID: P02918 Link_out
Gene: mrcA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Penicillin-binding protein 1B

Pharmacological action: yes
Actions: inhibitor

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)

Organism class: bacterial
UniProt ID: P02919 Link_out
Gene: mrcB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Penicillin-binding protein 2

Pharmacological action: yes
Actions: inhibitor

Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. Its synthesize cross- linked peptidoglycan from the lipid intermediates

Organism class: bacterial
UniProt ID: P0AD65 Link_out
Gene: mrdA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: substrate, inhibitor

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

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
  6. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
Comments
Drug created on July 23, 2007 07:06 / Updated on April 19, 2011 15:10

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.