DrugBank: Cefamandole (DB01326)

targets (1) transporters (4)

Identification

Name

Cefamandole

Accession Number

DB01326

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Cefadole
Cefamandole nafate

Salts

Not Available

Brand names

Name	Company
Mandol

Brand mixtures

Not Available

Categories

Anti-Bacterial Agents
Cephalosporins

CAS number

34444-01-4

Weight

Average: 462.503
Monoisotopic: 462.078009096

Chemical Formula

C₁₈H₁₈N₆O₅S₂

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Benzyl Alcohols and Derivatives
Phenethylamines
Cephalosporins

Substructures

Ethers
Hydroxy Compounds
Benzyl Alcohols and Derivatives
Acetates
Amino Ketones
Carboxylic Acids and Derivatives
Benzene and Derivatives
Aliphatic and Aryl Amines
Beta Lactams
Enamines
Tetrazoles
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Cephalosporins
Lactams
Azetidines
Cyanamides
Alcohols and Polyols

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.

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

Pharmacoeconomics

Manufacturers

Eli lilly and co

Packagers

Not Available

Dosage forms

Form	Route	Strength
Solution	Parenteral

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
logP	0.50	SANGSTER (1994)

Predicted Properties

Property	Value	Source
water solubility	5.81e-01 g/l	ALOGPS
logP	-0.05	ALOGPS
logP	0.027	ChemAxon
logS	-2.9	ALOGPS
pKa (strongest acidic)	3.32	ChemAxon
pKa (strongest basic)	-1.7	ChemAxon
physiological charge	-1	ChemAxon
hydrogen acceptor count	8	ChemAxon
hydrogen donor count	3	ChemAxon
polar surface area	150.54	ChemAxon
rotatable bond count	7	ChemAxon
refractivity	126.65	ChemAxon
polarizability	42.45	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D02344
KEGG Compound	C06879
PubChem Compound	456255
PubChem Substance	46508882
ChemSpider	401748
ChEBI	3480
ChEMBL	3480
Therapeutic Targets Database	DAP000448
PharmGKB	PA448837
RxList	http://www.rxlist.com/cgi/generic/cefamandole.htm
Wikipedia	http://en.wikipedia.org/wiki/Cefamandole

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Amikacin	Increased risk of nephrotoxicity
Gentamicin	Increased risk of nephrotoxicity
Netilmicin	Increased risk of nephrotoxicity
Probenecid	Probenecid may increase the serum level of cefamandole.
Tobramycin	Increased risk of nephrotoxicity

Food Interactions

Not Available

Targets
1. Penicillin-binding protein 2 Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: Q70KI2 Gene: pbpA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Targets

1. Penicillin-binding protein 2

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q70KI2 Link_out

Gene: pbpA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Transporters
1. Solute carrier family 22 member 6 Actions: inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 2. Solute carrier family 22 member 8 Actions: inhibitor 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) UniProt ID: Q8TCC7 Gene: SLC22A8 Protein Sequence: FASTA SNPs: SNPJam Report References: 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 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 3. Solute carrier family 22 member 11 Actions: inhibitor Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds UniProt ID: Q9NSA0 Gene: SLC22A11 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 4. Solute carrier family 22 member 7 Actions: inhibitor 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 UniProt ID: Q9Y694 Gene: SLC22A7 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

2. Solute carrier family 22 member 8

Actions: inhibitor

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)

UniProt ID: Q8TCC7 Link_out

Gene: SLC22A8 Link_out

Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out

Gene: SLC22A11 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

4. Solute carrier family 22 member 7

Actions: inhibitor

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

UniProt ID: Q9Y694 Link_out

Gene: SLC22A7 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 30, 2007 11:22 / Updated on February 08, 2013 16:20