Identification

Name
Cefditoren
Accession Number
DB01066  (APRD00850)
Type
Small Molecule
Groups
Approved, Investigational
Description

Cefditoren is a third-generation cephalosporin antibiotic for oral use. It is commonly marketed under the trade name Spectracef by Cornerstone BioPharma.

Structure
Thumb
Synonyms
  • Cefditoreno
Product Ingredients
IngredientUNIICASInChI Key
Cefditoren pivoxil78THA212DH117467-28-4AFZFFLVORLEPPO-UVYJNCLZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cefditoren PivoxilTablet, film coated400 mg/1OralPharma Rom Lev Inc.2010-01-01Not applicableUs
Cefditoren PivoxilTablet, film coated400 mg/1OralAristos Phamaceuticals, Inc.2010-01-012014-03-31Us
Cefditoren PivoxilTablet, film coated200 mg/1OralPharma Rom Lev Inc.2013-02-12Not applicableUs
Cefditoren PivoxilTablet, film coated200 mg/1OralAristos Phamaceuticals, Inc.2010-01-012014-03-31Us
SpectracefTablet, film coated200 mg/1OralVansen Pharma Inc.2013-02-05Not applicableUs
SpectracefTablet, film coated400 mg/1OralCornerstone Therapeutics Inc.2008-07-212014-03-31Us
SpectracefTablet, film coated400 mg/1OralVansen Pharma Inc.2013-02-05Not applicableUs
SpectracefTablet, film coated200 mg/1OralCornerstone Therapeutics Inc.2008-07-212014-03-31Us
International/Other Brands
Meiact
Categories
UNII
81QS09V3YW
CAS number
104145-95-1
Weight
Average: 506.578
Monoisotopic: 506.050079786
Chemical Formula
C19H18N6O5S3
InChI Key
KMIPKYQIOVAHOP-YLGJWRNMSA-N
InChI
InChI=1S/C19H18N6O5S3/c1-8-11(33-7-21-8)4-3-9-5-31-17-13(16(27)25(17)14(9)18(28)29)23-15(26)12(24-30-2)10-6-32-19(20)22-10/h3-4,6-7,13,17H,5H2,1-2H3,(H2,20,22)(H,23,26)(H,28,29)/b4-3-,24-12-/t13-,17-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(\C=C/C3=C(C)N=CS3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O

Pharmacology

Indication

For the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of microorganisms in acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, pharyngitis/tonsillitis, and uncomplicated skin and skin-structure infections.

Associated Conditions
Pharmacodynamics

Cefditoren pivoxil is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. Cefditoren is effective against Staphylococcus aureus (methicillin-susceptible strains, including b-lactamase-producing strains), penicillin-susceptible strains of Staphylococcus aureus and Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae (including b-lactamase-producing strains), Haemophilus parainfluenzae (including b-lactamase-producing strains), Moraxella catarrhalis (including b-lactamase-producing strains), Streptococcus agalactiae, Streptococcus Groups C and G, and Streptococcus, viridans group (penicillin-susceptible and -intermediate strains).

Mechanism of action

The bactericidal activity of cefditoren results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefditoren is stable in the presence of a variety of b-lactamases, including penicillinases and some cephalosporinases.

TargetActionsOrganism
APenicillin-binding protein 2B
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
Absorption

Following oral administration, cefditoren pivoxil is absorbed from the gastrointestinal tract and hydrolyzed to cefditoren by esterases. Under fasting conditions, the estimated absolute bioavailability of cefditoren pivoxil is approximately 14%. The absolute bioavailability of cefditoren pivoxil administered with a low fat meal (693 cal, 14 g fat, 122 g carb, 23 g protein) is 16.1 ± 3.0%.

Volume of distribution
  • 9.3 ± 1.6 L
Protein binding

Binding of cefditoren to plasma proteins averages 88% from in vitro determinations, and is concentration-independent at cefditoren concentrations ranging from 0.05 to 10 mg/mL.

Metabolism

Hydrolysis of cefditoren pivoxil to its active component, cefditoren, results in the formation of pivalate. Cefditoren is not appreciably metabolized.

Route of elimination

Pivalate is mainly eliminated (>99%) through renal excretion, nearly exclusively as pivaloylcarnitine.

Half life

Mean terminal elimination half-life is 1.6 ± 0.4 hours in young healthy adults.

Clearance
  • renal cl=4-5 L/h [oral administration]
Toxicity

Information on cefditoren pivoxil overdosage in humans is not available. However, with other b-lactam antibiotics, adverse effects following overdosage have included nausea, vomiting, epigastric distress, diarrhea, and convulsions. In acute animal toxicity studies, cefditoren pivoxil when tested at the limit oral doses of 5100 mg/kg in rats and up to 2000 mg/kg in dogs did not exhibit any health effects of concern.

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 Cefditoren is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Cefditoren is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Cefditoren is combined with 4-hydroxycoumarin.
AbacavirCefditoren may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseCefditoren may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacCefditoren may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Cefditoren is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Cefditoren is combined with Acenocoumarol.
AcetaminophenCefditoren may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Cefditoren.
Food Interactions
  • Antacids may reduce the serum concentration of cefditoren. Consider alternative methods to minimize/control acid reflux. If use of antacids cannot be avoided, separate administration by at least several hours to reduce chance of interaction

References

Synthesis Reference

Kiyoshi Yasui, Masahiro Onodera, Masamichi Sukegawa, Tatsuo Watanabe, Yuichi Yamamoto, Yasushi Murai, Katsuharu Iinuma, "Crystalline substance of cefditoren pivoxyl and the production of the same." U.S. Patent US6294669, issued March, 1986.

US6294669
General References
  1. Tempera G, Furneri PM, Carlone NA, Cocuzza C, Rigoli R, Musumeci R, Pilloni AP, Prenna M, Tufano MA, Tullio V, Vitali LA, Nicoletti G: Antibiotic susceptibility of respiratory pathogens recently isolated in Italy: focus on cefditoren. J Chemother. 2010 Jun;22(3):153-9. [PubMed:20566418]
External Links
Human Metabolome Database
HMDB0015199
KEGG Drug
D01628
PubChem Compound
9870843
PubChem Substance
46505471
ChemSpider
8046534
ChEBI
59343
ChEMBL
CHEMBL454446
Therapeutic Targets Database
DAP000444
PharmGKB
PA164747187
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Cefditoren
ATC Codes
J01DD16 — Cefditoren
FDA label
Download (200 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentUrinary Tract Infections (UTIs)1
4Unknown StatusTreatmentAcute maxillary sinusitis caused by M. catarrhalis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Aristos Pharmaceuticals
  • Ceph International Corp.
  • Cornerstone Pharmacy
  • Purdue Pharma LP
  • Tedec Meiji Farma S A
Dosage forms
FormRouteStrength
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral400 mg/1
Prices
Unit descriptionCostUnit
Spectracef 28 400 mg tablet Disp Pack476.99USD disp
Spectracef 20 200 mg tablet Disp Pack340.7USD disp
Spectracef 20 400 mg tablet Disp Pack340.7USD disp
Spectracef 200 mg dose pack tablet16.38USD tablet
Spectracef 400 mg dose pack tablet16.38USD tablet
Cefditoren pivoxil 400 mg tablet14.74USD tablet
Spectracef 200 mg tablet6.26USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5958915No1999-09-282016-10-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)127-129 °CNot Available
water solubilitySoluble at levels equal to < 0.1 mg/mL.Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0441 mg/mLALOGPS
logP1.7ALOGPS
logP-0.15ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)3.4ChemAxon
pKa (Strongest Basic)4.22ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area160.1 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity124.18 m3·mol-1ChemAxon
Polarizability49.19 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6124
Blood Brain Barrier-0.9894
Caco-2 permeable-0.7369
P-glycoprotein substrateSubstrate0.6427
P-glycoprotein inhibitor INon-inhibitor0.9042
P-glycoprotein inhibitor IINon-inhibitor0.7141
Renal organic cation transporterNon-inhibitor0.8873
CYP450 2C9 substrateNon-substrate0.8481
CYP450 2D6 substrateNon-substrate0.8288
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7687
CYP450 2C9 inhibitorNon-inhibitor0.7816
CYP450 2D6 inhibitorNon-inhibitor0.892
CYP450 2C19 inhibitorNon-inhibitor0.7665
CYP450 3A4 inhibitorNon-inhibitor0.7867
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9431
Ames testNon AMES toxic0.7987
CarcinogenicityNon-carcinogens0.8588
BiodegradationNot ready biodegradable0.984
Rat acute toxicity1.8714 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.8831
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 / 4,5-disubstituted thiazoles / 1,3-thiazines / 2-amino-1,3-thiazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Amino acids / Azetidines
show 10 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / 2,4-disubstituted 1,3-thiazole / 4,5-disubstituted 1,3-thiazole / Meta-thiazine / 1,3-thiazol-2-amine / Azole / Tertiary carboxylic acid amide / Thiazole
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin, carboxylic acid (CHEBI:59343)

Targets

Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Not Available
Specific Function
Penicillin binding
Gene Name
penA
Uniprot ID
P0A3M6
Uniprot Name
Penicillin-binding protein 2B
Molecular Weight
73872.305 Da
References
  1. Yamada M, Watanabe T, Miyara T, Baba N, Saito J, Takeuchi Y, Ohsawa F: Crystal structure of cefditoren complexed with Streptococcus pneumoniae penicillin-binding protein 2X: structural basis for its high antimicrobial activity. Antimicrob Agents Chemother. 2007 Nov;51(11):3902-7. Epub 2007 Aug 27. [PubMed:17724158]
Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
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
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Martin SI, Kaye KM: Beta-lactam antibiotics: newer formulations and newer agents. Infect Dis Clin North Am. 2004 Sep;18(3):603-19, ix. [PubMed:15308278]

Drug created on June 13, 2005 07:24 / Updated on November 05, 2018 17:48