Identification

Name
Ceftibuten
Accession Number
DB01415
Type
Small Molecule
Groups
Approved, Investigational
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.

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 IDs
7432-S / SCH 39720
Product Ingredients
IngredientUNIICASInChI Key
Ceftibuten dihydrate62F4443RWP118081-34-8SSWTVBYDDFPFAF-DKOGRLLHSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CedaxCapsule400 mg/1OralShionogi USA, Inc.1995-12-012011-06-30Us
CedaxSuspension180 mg/5mLOralPernix Therapeutics2010-10-202017-12-31Us
CedaxCapsule400 mg/1OralSciele Pharma, Inc.1995-12-20Not applicableUs
CedaxCapsule400 mg/1OralPernix Therapeutics1995-12-202017-12-31Us
CedaxSuspension90 mg/5mLOralShionogi USA, Inc.1995-12-012011-06-30Us
CedaxSuspension18 mg/1mLOralSciele Pharma, Inc.1995-12-20Not applicableUs
CedaxSuspension90 mg/5mLOralPernix Therapeutics1995-12-202012-08-01Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CeftibutenCapsule400 mg/1OralMacoven Pharmaceuticals2013-10-012017-12-31Us
CeftibutenSuspension180 mg/5mLOralMacoven Pharmaceuticals2013-10-012017-12-31Us
Categories
UNII
IW71N46B4Y
CAS number
97519-39-6
Weight
Average: 410.425
Monoisotopic: 410.03547558
Chemical Formula
C15H14N4O6S2
InChI Key
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
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

Pharmacology

Indication

Used to treat acute bacterial exacerbations of chronic bronchitis (ABECB), acute bacterial otitis media, pharyngitis, and tonsilitis.

Associated Conditions
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.

TargetActionsOrganism
APeptidoglycan synthase FtsI
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Ceftibuten is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Ceftibuten is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Ceftibuten is combined with 4-hydroxycoumarin.
AbacavirCeftibuten may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseCeftibuten may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacCeftibuten may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ceftibuten which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Ceftibuten is combined with Acenocoumarol.
AcetaminophenCeftibuten may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe excretion of Ceftibuten can be decreased when combined with Acetazolamide.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015485
KEGG Drug
D00922
KEGG Compound
C08117
PubChem Compound
5282242
PubChem Substance
46507324
ChemSpider
4445419
BindingDB
50370586
ChEBI
3510
ChEMBL
CHEMBL1605
Therapeutic Targets Database
DAP000456
PharmGKB
PA164744555
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ceftibuten
ATC Codes
J01DD14 — Ceftibuten

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
3TerminatedTreatmentPyelonephritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Schering Corp.
  • Sciele Pharma Inc.
  • Shionogi Pharma Inc.
  • Zyber Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral400 mg/1
SuspensionOral18 mg/1mL
SuspensionOral90 mg/5mL
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)
US5599557No1997-02-042014-02-04Us
US4634697No1987-01-062009-10-01Us

Properties

State
Solid
Experimental Properties
Not 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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 / Dicarboxylic acids and derivatives / N-acyl amines / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Amino acids
show 10 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / 2,4-disubstituted 1,3-thiazole / Meta-thiazine / N-acyl-amine / Dicarboxylic acid or derivatives / 1,3-thiazol-2-amine / Azole / Tertiary carboxylic acid amide
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin, dicarboxylic acid (CHEBI:3510)

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 fr...
Gene Name
ftsI
Uniprot ID
P0AD68
Uniprot Name
Peptidoglycan synthase FtsI
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 str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
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 str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
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
Uniprot Name
Penicillin-binding protein 2
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
Substrate
Inhibitor
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. 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
Uniprot Name
Solute carrier family 15 member 2
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Substrate profile was investigated in 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 was investigated 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 July 23, 2007 07:06 / Updated on November 02, 2018 08:48