Identification

Name
Cefotiam
Accession Number
DB00229  (APRD00855)
Type
Small Molecule
Groups
Approved, Investigational
Description

One of the cephalosporins that has a broad spectrum of activity against both gram-positive and gram-negative microorganisms. [PubChem]

Structure
Thumb
Synonyms
  • (6R,7R)-7-[2-(2-Amino-thiazol-4-yl)-acetylamino]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • CEFOTIAM
  • Cefotiamum
  • CTM
External IDs
J01DC07
Product Ingredients
IngredientUNIICASInChI Key
Cefotiam hydrochlorideH7V12WDZ9366309-69-1SVSFIELZISOJDT-XRZFDKQNSA-N
International/Other Brands
Ceradon / Pansporin (Takeda Pharmaceutical)
Categories
UNII
91W6Z2N718
CAS number
61622-34-2
Weight
Average: 525.628
Monoisotopic: 525.103512339
Chemical Formula
C18H23N9O4S3
InChI Key
QYQDKDWGWDOFFU-IUODEOHRSA-N
InChI
InChI=1S/C18H23N9O4S3/c1-25(2)3-4-26-18(22-23-24-26)34-7-9-6-32-15-12(14(29)27(15)13(9)16(30)31)21-11(28)5-10-8-33-17(19)20-10/h8,12,15H,3-7H2,1-2H3,(H2,19,20)(H,21,28)(H,30,31)/t12-,15-/m1/s1
IUPAC Name
(6R,7R)-7-[2-(2-amino-1,3-thiazol-4-yl)acetamido]-3-[({1-[2-(dimethylamino)ethyl]-1H-1,2,3,4-tetrazol-5-yl}sulfanyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(CSC3=NN=NN3CCN(C)C)=C(N1C(=O)[C@H]2NC(=O)CC1=CSC(N)=N1)C(O)=O

Pharmacology

Indication

For treatment of severe infections caused by susceptible bacteria.

Pharmacodynamics

Cefotiam is a third generation beta-lactam cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. Cefotiam works by inhibiting bacterial cell wall biosynthesis.

Mechanism of action

The bactericidal activity of cefotiam results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

TargetActionsOrganism
APenicillin-binding protein 1A
inducer
Clostridium perfringens (strain 13 / Type A)
Absorption

Rapidly absorbed following intramuscular injection. Bioavailability is 60% following intramuscular injection.

Volume of distribution
Not Available
Protein binding

40%

Metabolism
Not Available
Route of elimination
Not Available
Half life

Approximately 1 hour.

Clearance
Not Available
Toxicity

Adverse effects following overdosage include nausea, vomiting, epigastric distress, diarrhea, and 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 Cefotiam is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Cefotiam is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Cefotiam is combined with 4-hydroxycoumarin.
AbacavirCefotiam may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Cefotiam.
AcarboseCefotiam may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacCefotiam 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 Cefotiam is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding can be increased when Cefotiam is combined with Acenocoumarol.
AcetaminophenCefotiam may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Muller R, Bottger C, Wichmann G: Suitability of cefotiam and cefuroxime axetil for the perioperative short-term prophylaxis in tonsillectomy patients. Arzneimittelforschung. 2003;53(2):126-32. [PubMed:12642969]
  2. Kolben M, Mandoki E, Ulm K, Freitag K: Randomized trial of cefotiam prophylaxis in the prevention of postoperative infectious morbidity after elective cesarean section. Eur J Clin Microbiol Infect Dis. 2001 Jan;20(1):40-2. [PubMed:11245321]
  3. Shimizu S, Chen KR, Miyakawa S: Cefotiam-induced contact urticaria syndrome: an occupational condition in Japanese nurses. Dermatology. 1996;192(2):174-6. [PubMed:8829507]
External Links
Human Metabolome Database
HMDB0014374
KEGG Drug
D01819
PubChem Compound
43708
PubChem Substance
46506679
ChemSpider
39831
ChEBI
355510
ChEMBL
CHEMBL1296
Therapeutic Targets Database
DAP001177
PharmGKB
PA164749298
Wikipedia
Cefotiam
ATC Codes
J01DC07 — Cefotiam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableActive Not RecruitingPreventionGastric Varices / Liver Cirrhosis1
Not AvailableRecruitingPreventionGastric Varices / Liver Cirrhosis1

Pharmacoeconomics

Manufacturers
  • Takeda chemical industries ltd
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP-2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.29 mg/mLALOGPS
logP-0.33ALOGPS
logP-3.1ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)2.79ChemAxon
pKa (Strongest Basic)8.36ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area172.46 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity142.34 m3·mol-1ChemAxon
Polarizability49.87 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5528
Blood Brain Barrier-0.9865
Caco-2 permeable-0.6981
P-glycoprotein substrateSubstrate0.9008
P-glycoprotein inhibitor INon-inhibitor0.7087
P-glycoprotein inhibitor IINon-inhibitor0.92
Renal organic cation transporterNon-inhibitor0.8475
CYP450 2C9 substrateNon-substrate0.8441
CYP450 2D6 substrateNon-substrate0.8071
CYP450 3A4 substrateSubstrate0.568
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8496
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7105
Ames testNon AMES toxic0.6519
CarcinogenicityNon-carcinogens0.9074
BiodegradationNot ready biodegradable0.7808
Rat acute toxicity2.4511 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.891
hERG inhibition (predictor II)Non-inhibitor0.806
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 / Alkylarylthioethers / 1,3-thiazines / 2-amino-1,3-thiazoles / Tetrazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Trialkylamines / Azetidines
show 13 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Aryl thioether / 2,4-disubstituted 1,3-thiazole / Alkylarylthioether / Meta-thiazine / 1,3-thiazol-2-amine / Azole / Heteroaromatic compound
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin, semisynthetic derivative (CHEBI:355510)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inducer
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. Matsuda K, Nakamura K, Adachi Y, Inoue M, Kawakami M: Autolysis of methicillin-resistant Staphylococcus aureus is involved in synergism between imipenem and cefotiam. Antimicrob Agents Chemother. 1995 Dec;39(12):2631-4. [PubMed:8592992]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate activity towards rat OAT1 was suggested in vitro studies using Xenopus laevis.
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. Uwai Y, Saito H, Inui K: Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone. Drug Metab Pharmacokinet. 2002;17(2):125-9. [PubMed:15618660]
  2. 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 activity was demonstrated 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 June 13, 2005 07:24 / Updated on November 02, 2018 08:41