Identification

Name
Cefamandole
Accession Number
DB01326
Type
Small Molecule
Groups
Approved, Investigational
Description

Cefamandole (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 IDs
J01DC03
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mandol Add-vantage Inj 1gm/vialPowder, for solution1 gIntravenousEli Lilly & Co. Ltd.1989-12-311998-08-04Canada
Mandol Inj 1gm/ampPowder, for solution1 gIntramuscular; IntravenousEli Lilly & Co. Ltd.1978-12-312000-10-02Canada
Mandol Inj 2gm/ampPowder, for solution2 gIntravenousEli Lilly & Co. Ltd.1978-12-312000-08-03Canada
International/Other Brands
Kefadol (Lilly) / Kefandol (Lilly) / Mandokef (Lilly) / Mandol (Lilly)
Categories
UNII
5CKP8C2LLI
CAS number
34444-01-4
Weight
Average: 462.503
Monoisotopic: 462.078009096
Chemical Formula
C18H18N6O5S2
InChI Key
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)[C@H]2NC(=O)[C@H](O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

For the treatment of serious infections caused by susceptible strains of microorganisms.

Pharmacodynamics

Cefamandole 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 action

Like 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.

TargetActionsOrganism
APenicillin-binding protein 2
inhibitor
Bacteroides fragilis
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

75%

Metabolism
Not Available
Route of elimination
Not Available
Half life

The half-life after an intravenous dose is 32 minutes; after intramuscular administration, the half-life is 60 minutes.

Clearance
Not Available
Toxicity

Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcenocoumarolCefamandole may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenCefamandole 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 Cefamandole is combined with Acetylsalicylic acid.
AlprazolamCefamandole may decrease the excretion rate of Alprazolam which could result in a higher serum level.
AmikacinThe risk or severity of nephrotoxicity can be increased when Cefamandole is combined with Amikacin.
AmlodipineCefamandole may decrease the excretion rate of Amlodipine which could result in a higher serum level.
AmoxicillinCefamandole may decrease the excretion rate of Amoxicillin which could result in a higher serum level.
AmphetamineCefamandole may decrease the excretion rate of Amphetamine which could result in a higher serum level.
AmpicillinCefamandole may decrease the excretion rate of Ampicillin which could result in a higher serum level.
ApramycinCefamandole may increase the nephrotoxic activities of Apramycin.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0015421
KEGG Drug
D02344
KEGG Compound
C06879
PubChem Compound
456255
PubChem Substance
46508882
ChemSpider
401748
BindingDB
50350468
ChEBI
3480
ChEMBL
CHEMBL1146
Therapeutic Targets Database
DAP000448
PharmGKB
PA448837
HET
SMX
RxList
RxList Drug Page
Wikipedia
Cefamandole
ATC Codes
J01DC03 — Cefamandole
PDB Entries
3ny4

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
Not AvailableNot Yet RecruitingNot AvailableCommunity Acquired Pneumonia (CAP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous1 g
Powder, for solutionIntramuscular; Intravenous1 g
Powder, for solutionIntravenous2 g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)182-184Greene, 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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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 / Phenylacetamides / Alkylarylthioethers / 1,3-thiazines / Tetrazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azetidines / Secondary carboxylic acid amides / Secondary alcohols
show 12 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Phenylacetamide / Aryl thioether / Alkylarylthioether / Benzenoid / Meta-thiazine / Monocyclic benzene moiety / Heteroaromatic compound
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin, semisynthetic derivative (CHEBI:3480)

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
Uniprot Name
Penicillin-binding protein 2
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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
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
Uniprot Name
Solute carrier family 22 member 11
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 sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
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]

Drug created on June 30, 2007 11:22 / Updated on August 02, 2018 04:34