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

Similar Structures

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
Céfamandole
Cefamandole
Cefamandolum
Cephadole
Cephamandole
L-Cefamandole

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Mandol Add-vantage Inj 1gm/vial	Powder, for solution	1 g	Intravenous	Eli Lilly & Co. Ltd.	1989-12-31	1998-08-04

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.

Target	Actions	Organism
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

Drug	Interaction
(R)-warfarin	The risk or severity of bleeding can be increased when Cefamandole is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Cefamandole is combined with (S)-Warfarin.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Cefamandole is combined with 4-hydroxycoumarin.
Abacavir	Cefamandole may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abciximab	The therapeutic efficacy of Abciximab can be decreased when used in combination with Cefamandole.
Acarbose	Cefamandole may decrease the excretion rate of Acarbose which could result in a higher serum level.
Aceclofenac	Cefamandole may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
Acemetacin	The risk or severity of nephrotoxicity can be increased when Cefamandole is combined with Acemetacin.
Acenocoumarol	The risk or severity of bleeding can be increased when Cefamandole is combined with Acenocoumarol.
Acetaminophen	Cefamandole may decrease the excretion rate of Acetaminophen which could result in a higher serum level.

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

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Osteomyelitis	1
Not Available	Not Yet Recruiting	Not Available	Community Acquired Pneumonia (CAP)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Powder, for solution	Intravenous	1 g

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	182-184	Greene, J.M. and Indelicato, J.M.; US. Patent 3,928,592; December 23,1975; assigned to Eli Lilly & Co.
logP	0.50	SANGSTER (1994)

Predicted Properties

Property	Value	Source
Water Solubility	0.581 mg/mL	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 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	126.65 m³·mol^-1	ChemAxon
Polarizability	42.45 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8573
Blood Brain Barrier	-	0.9918
Caco-2 permeable	-	0.795
P-glycoprotein substrate	Substrate	0.769
P-glycoprotein inhibitor I	Non-inhibitor	0.8401
P-glycoprotein inhibitor II	Non-inhibitor	0.8066
Renal organic cation transporter	Non-inhibitor	0.8467
CYP450 2C9 substrate	Non-substrate	0.7367
CYP450 2D6 substrate	Non-substrate	0.822
CYP450 3A4 substrate	Substrate	0.5185
CYP450 1A2 substrate	Non-inhibitor	0.8336
CYP450 2C9 inhibitor	Non-inhibitor	0.7509
CYP450 2D6 inhibitor	Non-inhibitor	0.8653
CYP450 2C19 inhibitor	Non-inhibitor	0.7454
CYP450 3A4 inhibitor	Non-inhibitor	0.7111
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.5818
Ames test	Non AMES toxic	0.7075
Carcinogenicity	Non-carcinogens	0.9222
Biodegradation	Not ready biodegradable	0.8565
Rat acute toxicity	2.2075 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9594
hERG inhibition (predictor II)	Non-inhibitor	0.5988

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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

Details1. Penicillin-binding protein 2

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

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

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	30	N/A	N/A	11909604

Details1. Solute carrier family 22 member 6

Kind: Protein
Organism: Humans
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

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]
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]
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]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	46	N/A	N/A	11909604

Details2. Solute carrier family 22 member 8

Kind: Protein
Organism: Humans
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

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]
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]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1140	N/A	N/A	11909604

Details3. Solute carrier family 22 member 11

Kind: Protein
Organism: Humans
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

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]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1570000	N/A	N/A	12650826

Details4. Solute carrier family 22 member 7

Kind: Protein
Organism: Humans
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

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 December 20, 2018 09:19

Cefamandole

Identification

Structure for Cefamandole (DB01326)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Transporters

References

References

References

References