DT-Web

DB01066 - Cefditoren


Identification
Name Cefditoren
Accession Number DB01066 (APRD00850)
Type small molecule
Description Cefditoren is a third-generation cephalosporin antibiotic for oral use. It is commonly marketed under the trade name Spectracef by Cornerstone BioPharma.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 506.578
Groups approved
Monoisotopic Weight 506.050079786
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.
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.
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%.
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.
Biotransformation 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.
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
Interactions
Drug Interactions
Drug Mechanism of interaction
Cimetidine H2-Antagonists such as cimetidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.
Esomeprazole Proton pump inhibitors such as esomeprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
Famotidine H2-Antagonists such as famotidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.
Lansoprazole Proton pump inhibitors such as lansoprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
Nizatidine H2-Antagonists such as nizatidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.
Omeprazole Proton pump inhibitors such as omeprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
Pantoprazole Proton pump inhibitors such as pantoprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
Rabeprazole Proton pump inhibitors such as rabeprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.
Ranitidine H2-Antagonists such as ranitidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.
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

Targets


Penicillin-binding protein 2B
Name Penicillin-binding protein 2B
Gene Name penA
Pharmacological action yes
Actions inhibitor
References
  • 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
DTHybrid score 0.0126
Penicillin-binding proteins 1A/1B
Name Penicillin-binding proteins 1A/1B
Gene Name pbpA
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 0.7936

Predictions


Id Partner name Gene Name Score
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.1502
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.1428
1729 Solute carrier family 22 member 6 SLC22A6 0.0865
118 Organic cation/carnitine transporter 2 SLC22A5 0.0488
6113 MecA PBP2' (penicillin binding protein 2') mecA 0.0443
1 Peptidoglycan synthetase ftsI ftsI 0.0406
4155 Peptidoglycan synthetase ftsI ftsI 0.0406
115 Penicillin-binding protein 2 mrdA 0.0351
6069 Penicillin-binding protein 2 mrdA 0.0351
6118 Penicillin-binding protein 2 penA 0.0351
6187 Penicillin-binding protein 2 pbpA 0.0351
6686 Penicillin-binding protein 2 pbp2 0.0351
6939 Penicillin-binding protein 2 mrdA 0.0351
7163 Penicillin-binding protein 2 pbpA 0.0351
6142 Solute carrier family 22 member 8 SLC22A8 0.0345
2461 D-alanyl-D-alanine carboxypeptidase Not Available 0.0285
5756 D-alanyl-D-alanine carboxypeptidase dac 0.0285
1024 Solute carrier family 22 member 11 SLC22A11 0.0284
4512 Cytochrome P450 3A4 CYP3A4 0.0273
587 Serum albumin ALB 0.0249
819 Penicillin-binding protein 4 dacB 0.0233
2385 Penicillin acylase Not Available 0.0166
6067 Penicillin binding protein 2a mecA 0.0143
1757 Myeloperoxidase MPO 0.0139
332 Beta-lactamase blaZ 0.0133
2478 Beta-lactamase ampC 0.0133
2613 Beta-lactamase ampC 0.0133
2635 Beta-lactamase ampC 0.0133
2700 Beta-lactamase penP 0.0133
5445 Beta-lactamase blaB 0.0133
6019 Beta-lactamase SHV-7 0.0133
6701 Beta-lactamase cphA 0.0133
6143 Solute carrier family 22 member 7 SLC22A7 0.0127
159 Penicillin-binding protein 2B penA 0.0126
4252 Penicillin-binding protein 5 dacA 0.0117
3426 Glutamine synthetase glnA 0.0097
3987 Glutamine synthetase GLUL 0.0097
3760 Penicillin-binding protein 5 precursor dacA 0.0095
867 Penicillin-binding protein 3 pbpC 0.0094
6119 Penicillin-binding protein 3 pbp3 0.0094
7154 Penicillin-binding protein 3 pbp3 0.0094
7157 Penicillin-binding protein 3 LMHCC_2184 0.0094
7162 Penicillin-binding protein 3 pbpB 0.0094
7172 Penicillin-binding protein 3 pbp3 0.0094
6184 D-alanyl-D-alanine carboxypeptidase dacC dacC 0.0091
738 Monocarboxylate transporter 1 SLC16A1 0.0077
543 Penicillin-binding protein 1B mrcB 0.0075
6186 Penicillin-binding protein 1B ponB 0.0075
6822 Penicillin-binding protein 1b pbp1b 0.0075
6844 Penicillin-binding protein 1b pbp1b 0.0075
645 Penicillin-binding protein 1A mrcA 0.0074
5805 Penicillin-binding protein 1A ponA 0.0074
6185 Penicillin-binding protein 1A mrcA 0.0074
6799 Penicillin-binding protein 1A pbpA 0.0074
6016 Cytochrome P450 2C19 CYP2C19 0.0067
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0065
4200 Cytochrome P450 1A2 CYP1A2 0.0063
4119 Cytochrome P450 2D6 CYP2D6 0.003
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