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Identification
NameCefamandole
Accession NumberDB01326
TypeSmall Molecule
GroupsApproved
DescriptionCefamandole (INN, also known as cephamandole) is a broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is the formate ester cefamandole nafate, a prodrug which is administered parenterally. Cefamandole is no longer available in the United States.
Structure
Thumb
Synonyms
(6R,7R)-7-(R)-Mandelamido-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-carboxylic acid
(6R,7R)-7-{[(2R)-2-hydroxy-2-phenylacetyl]amino}-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Cefadole
Cefamandol
Cefamandole nafate
Cefamandolum
Cephadole
Cephamandole
L-Cefamandole
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mandol Add-vantage Inj 1gm/vialpowder for solution1 gintravenousEli Lilly Canada Inc1989-12-311998-08-04Canada
Mandol Inj 1gm/amppowder for solution1 gintramuscular; intravenousEli Lilly Canada Inc1978-12-312000-10-02Canada
Mandol Inj 2gm/amppowder for solution2 gintravenousEli Lilly Canada Inc1978-12-312000-08-03Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
KefadolLilly
KefandolLilly
MandokefLilly
MandolLilly
Brand mixturesNot Available
SaltsNot Available
Categories
UNII5CKP8C2LLI
CAS number34444-01-4
WeightAverage: 462.503
Monoisotopic: 462.078009096
Chemical FormulaC18H18N6O5S2
InChI KeyInChIKey=OLVCFLKTBJRLHI-AXAPSJFSSA-N
InChI
InChI=1S/C18H18N6O5S2/c1-23-18(20-21-22-23)31-8-10-7-30-16-11(15(27)24(16)12(10)17(28)29)19-14(26)13(25)9-5-3-2-4-6-9/h2-6,11,13,16,25H,7-8H2,1H3,(H,19,26)(H,28,29)/t11-,13-,16-/m1/s1
IUPAC Name
(6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-3-{[(1-methyl-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=NN3C)=C(N1C(=O)[[email protected]]2NC(=O)[[email protected]](O)C1=CC=CC=C1)C(O)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentCephalosporins
Alternative Parents
Substituents
  • Cephalosporin
  • N-acyl-alpha amino acid or derivatives
  • Phenylacetamide
  • Alpha-amino acid or derivatives
  • Alkylarylthioether
  • Benzenoid
  • Monocyclic benzene moiety
  • Meta-thiazine
  • Heteroaromatic compound
  • Tetrazole
  • Tertiary carboxylic acid amide
  • Azole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Sulfenyl compound
  • Hemithioaminal
  • Thioether
  • Monocarboxylic acid or derivatives
  • Enamine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of serious infections caused by susceptible strains of microorganisms.
PharmacodynamicsCefamandole is a broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is the formate ester cefamandole nafate, a prodrug which is administered parenterally. The bactericidal action of cefamandole results from inhibition of cell-wall synthesis. Cephalosporins have in vitro activity against a wide range of gram-positive and gram-negative organisms.
Mechanism of actionLike all beta-lactam antibiotics, cefamandole binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefamandole interferes with an autolysin inhibitor.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding75%
MetabolismNot Available
Route of eliminationNot Available
Half lifeThe half-life after an intravenous dose is 32 minutes; after intramuscular administration, the half-life is 60 minutes.
ClearanceNot Available
ToxicitySymptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8573
Blood Brain Barrier-0.9918
Caco-2 permeable-0.795
P-glycoprotein substrateSubstrate0.769
P-glycoprotein inhibitor INon-inhibitor0.8401
P-glycoprotein inhibitor IINon-inhibitor0.8066
Renal organic cation transporterNon-inhibitor0.8467
CYP450 2C9 substrateNon-substrate0.7367
CYP450 2D6 substrateNon-substrate0.822
CYP450 3A4 substrateSubstrate0.5185
CYP450 1A2 substrateNon-inhibitor0.8336
CYP450 2C9 inhibitorNon-inhibitor0.7509
CYP450 2D6 inhibitorNon-inhibitor0.8653
CYP450 2C19 inhibitorNon-inhibitor0.7454
CYP450 3A4 inhibitorNon-inhibitor0.7111
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5818
Ames testNon AMES toxic0.7075
CarcinogenicityNon-carcinogens0.9222
BiodegradationNot ready biodegradable0.8565
Rat acute toxicity2.2075 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9594
hERG inhibition (predictor II)Non-inhibitor0.5988
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Powder for solutionintravenous1 g
Powder for solutionintramuscular; intravenous1 g
Powder for solutionintravenous2 g
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point182-184Greene, J.M. and Indelicato, J.M.; US. Patent 3,928,592; December 23,1975; assigned to Eli Lilly & Co.
logP0.50SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.581 mg/mLALOGPS
logP-0.05ALOGPS
logP0.027ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)3.32ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area150.54 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity126.65 m3·mol-1ChemAxon
Polarizability42.45 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Ta Sen Chou, Gary D. Zintgraff, “Process for preparing pure cefamandole from alkali metal and ammonium salts thereof.” U.S. Patent US4115644, issued June, 1977.

US4115644
General ReferencesNot Available
External Links
ATC CodesJ01DC03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolCefamandole may increase the anticoagulant activities of Acenocoumarol.
DicoumarolCefamandole may increase the anticoagulant activities of Dicoumarol.
Ethyl biscoumacetateCefamandole may increase the anticoagulant activities of Ethyl biscoumacetate.
PhenindioneCefamandole may increase the anticoagulant activities of Phenindione.
PhenprocoumonCefamandole may increase the anticoagulant activities of Phenprocoumon.
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefamandole.
ProbenecidThe serum concentration of Cefamandole can be increased when it is combined with Probenecid.
WarfarinCefamandole may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Bacteroides fragilis
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
pbpA
Uniprot ID:
Q70KI2
Molecular Weight:
69434.305 Da
References
  1. Yotsuji A, Mitsuyama J, Hori R, Yasuda T, Saikawa I, Inoue M, Mitsuhashi S: Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis. Antimicrob Agents Chemother. 1988 Dec;32(12):1848-53. [PubMed:3266730 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. [PubMed:11909604 ]
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. [PubMed:12005172 ]
  3. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [PubMed:10411577 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. [PubMed:11909604 ]
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. [PubMed:12005172 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
References
  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. [PubMed:11909604 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. Eur J Pharmacol. 2003 Mar 28;465(1-2):1-7. [PubMed:12650826 ]
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Drug created on June 30, 2007 11:22 / Updated on August 17, 2016 12:23