CEFAMANDOLE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H18N6O5S2
Molecular Weight	462.503
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1N=NN=C1SCC2=C(N3[C@H](SC2)[C@H](NC(=O)[C@H](O)C4=CC=CC=C4)C3=O)C(O)=O

InChI

InChIKey=OLVCFLKTBJRLHI-AXAPSJFSSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm

Cefamandole (also known as cephamandole) is a broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is an ester form, cefamandole nafate, a prodrug. Cefamandole is no longer available in USA, but it has prescription in UK. Cefamandole under brand name mandol is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms such as: lower respiratory infections, including pneumonia, caused by S. pneumoniae. So as urinary tract infections caused by E. coli, Proteus spp.; peritonitis caused by E. coli and Enterobacter spp. Septicemia caused by E. coli; skin and skin structure infections caused by S. aureus; bone and joint infections caused by S. aureus (penicillinase- and non-penicillinase-producing). 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. Bacterial cell wall autolytic enzymes such as autolysins then mediate cell lysis; it is possible that cefamandole interferes with an autolysin inhibitor.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial penicillin-binding protein 234 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3266730	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Lower respiratory infections 3 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8583	MANDOL Approved Use Unknown Launch Date 1978
Urinary tract infections 207 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8583	MANDOL Approved Use Unknown Launch Date 1978
Peritonitis 22 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8583	MANDOL Approved Use Unknown Launch Date 1978
Sepsis 74 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8583	MANDOL Approved Use Unknown Launch Date 1978

C_max

Value	Dose	Co-administered	Analyte	Population
113 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/671221/	15 mg single, intravenous dose: 15 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CEFAMANDOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
5934 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/671221/	15 mg single, intravenous dose: 15 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CEFAMANDOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.64 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/671221/	15 mg single, intravenous dose: 15 mg route of administration: Intravenous experiment type: SINGLE co-administered:		CEFAMANDOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5.1 g 1 times / day multiple, intravenous Dose: 5.1 g, 1 times / day Route: intravenous Route: multiple Dose: 5.1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3718099	unhealthy, 43 - 58 years Health Status: unhealthy Age Group: 43 - 58 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3718099	Disc. AE: Hypoprothrombinemia... AEs leading to discontinuation/dose reduction: Hypoprothrombinemia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/3718099
2 g 6 times / day multiple, intravenous Highest studied dose Dose: 2 g, 6 times / day Route: intravenous Route: multiple Dose: 2 g, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/	Other AEs: Glutamic-oxaloacetic transaminase increased, Lactic dehydrogenase increased... Other AEs: Glutamic-oxaloacetic transaminase increased (20%) Lactic dehydrogenase increased (20%) Alkaline phosphatase increased (20%) Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/
1 g single, intramuscular Dose: 1 g Route: intramuscular Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/426510	unhealthy Health Status: unhealthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/426510	Sources: https://pubmed.ncbi.nlm.nih.gov/426510

AEs

AE	Significance	Dose	Population
Hypoprothrombinemia	2 patients Disc. AE	5.1 g 1 times / day multiple, intravenous Dose: 5.1 g, 1 times / day Route: intravenous Route: multiple Dose: 5.1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3718099	unhealthy, 43 - 58 years Health Status: unhealthy Age Group: 43 - 58 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3718099
Alkaline phosphatase increased	20%	2 g 6 times / day multiple, intravenous Highest studied dose Dose: 2 g, 6 times / day Route: intravenous Route: multiple Dose: 2 g, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/
Glutamic-oxaloacetic transaminase increased	20%	2 g 6 times / day multiple, intravenous Highest studied dose Dose: 2 g, 6 times / day Route: intravenous Route: multiple Dose: 2 g, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/
Lactic dehydrogenase increased	20%	2 g 6 times / day multiple, intravenous Highest studied dose Dose: 2 g, 6 times / day Route: intravenous Route: multiple Dose: 2 g, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 150 OAT1 725 OAT2 153 OAT3 747

Drug as perpetrator

Target	Modality	Activity
OAT2 155	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1570 uM]
OAT4 150	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1140 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 30 uM]
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 50 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3480	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3480
ChemicalBook	CB2398185	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2398185
ZINC	ZINC000003830394	http://zinc15.docking.org/substances/ZINC000003830394

PubMed

Title	Date	PubMed
Comparison of thrombophlebitis associated with three cephalosporin antibiotics.	1976 Sep	791101
Cefamandole for treatment of obstetrical and gynecological infections.	1980	7010540
In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria.	1988 Dec	3243734
Occurrence and antibiotic resistance of mesophilic Aeromonas in three riverine freshwaters of Marrakech, Morocco.	2001 Dec 1	12805714
[Infectious complications of mandibular osteotomy].	2001 Feb	11345621
[Characterization of cefoperazone resistance gene on plasmid pFC in E. coli HX88108].	2001 Mar	12733347
Serotypes, virulence factors, antibiotic sensitivity, beta-lactamase activity and plasmid analysis of Salmonella from children with diarrhea in Tripoli (Libya).	2002	12512253
Cross-reactivity of cefotetan and ceftriaxone antibodies, associated with hemolytic anemia, with other: cephalosporins and penicillin.	2002 Aug	12162687
Review of the use of cephalosporins in children with anaphylactic reactions from penicillins.	2002 Jul	18159398
Practical aspects of choosing an antibiotic for patients with a reported allergy to an antibiotic.	2002 Jul 1	12060871
[Beta-lactam resistance in aquatic Enterobacter cloacae strains using phenotypic and genotypic criteria].	2002 Jul-Dec	15085610
beta-Lactam allergenic determinants: fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin.	2002 Nov	12569987
New polymer-antibiotic systems to inhibit bacterial biofilm formation: a suitable approach to prevent central venous catheter-associated infections.	2002 Oct	12462430
Kinetics of cefamandole nafate degradation in solid phase.	2003 Apr	12727540
Pharmacodynamics and pharmacokinetics of cefoperazone and cefamandole in dogs following single dose intravenous and intramuscular administration.	2003 Sep	12902182
The synergistic effect of EDTA/antimicrobial combinations on Pseudomonas aeruginosa.	2004	14723685
Effects of bovine lactoferrin hydrolysate on the in vitro antimicrobial susceptibility of Escherichia coli strains isolated from baby pigs.	2004 Feb	14974567
Escherichia coli producing CTX-M-2 beta-lactamase in cattle, Japan.	2004 Jan	15078599
Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins.	2004 Jul 6	15238366
Cardiac actinomycosis in a patient presenting with acute cardiac tamponade and a mass mimicking pericardial tumour.	2004 May	15084575
Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.	2004 Sep 14	15342186
IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient.	2006 Dec	17176412
Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses.	2006 Oct	16941232
Enzymatic synthesis of cephalosporins. The immobilized acylase from Arthrobacter viscosus: a new useful biocatalyst.	2007 Dec	17879093
Estimation of the two sample preparation techniques for infrared spectroscopic identification of Cefamandole nafate in solid state.	2007 Sep	17993089
New active site oriented glyoxyl-agarose derivatives of Escherichia coli penicillin G acylase.	2007 Sep 10	17845725
Superficial and deep sternal wound infection after more than 9000 coronary artery bypass graft (CABG): incidence, risk factors and mortality.	2007 Sep 23	17888179
Pharmacodynamic optimization of beta-lactams in the patient care setting.	2008	18495059
[Regional lymphotropic antibiotic therapy as a part of comprehensive treatment of children with purulent-inflammatory diseases of maxillofacial region].	2008	18454123
Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics.	2008 Jun	18339814
Spectrophotometeric Determination of Cefuroxime Axetil from bulk and in its tablet dosage form.	2008 Mar-Apr	20046725
Translocation of bacterial NOD2 agonist and its link with inflammation.	2009	19638210
Suspected anaphylactic reactions associated with anaesthesia.	2009 Feb	19143700
Prevalence and molecular characterization of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Riyadh, Saudi Arabia.	2009 Jul-Aug	19587523
Antibiotic prophylaxis for lung surgery: bronchial colonization is the critical issue?	2009 Sep	19699971

Patents

Sample Use Guides

In Vivo Use Guide

The usual dosage range for cefamandol (cefamandole) is 500 mg to 1 g every 4 to 8 hours. In infections of skin structures and in uncomplicated pneumonia, a dosage of 500 mg every 6 hours is adequate. In uncomplicated urinary tract infections, a dosage of 500 mg every 8 hours is sufficient. In more serious urinary tract infections, a dosage of 1 g every 8 hours may be needed. In severe infections, 1-g doses may be given at 4 to 6-hour intervals. In life-threatening infections or infections due to less susceptible organisms, doses up to 2 g every 4 hours (ie, 12 g/day) may be needed. Infants and Children: administration of 50 to 100 mg/kg/ day in equally divided doses every 4 to 8 hours has been effective for most infections susceptible to Mandol (cefamandole). This may be increased to a total daily dose of 150 mg/kg (not to exceed the maximum adult dose) for severe infections.

Route of Administration: Other

In Vitro Use Guide

The intracellular activity of cefamandole against phagocytosed Staphylococcus aureus was studied using a sensitive and standardized method of murine peritoneal macrophages. Cefamandole exerted an intracellular antibacterial activity against E. coli which was greater than their extracellular one. With concentrations of antibiotic up to 16 x MBC a dose-dependent decrease of the initial number of intracellular E. coli which ranged from 32% to 90% was observed. However, similar antibiotic concentrations above the MBC affected the viability of extracellular E. coli by only 20% to 30%. The intracellular antibacterial activity of antibiotic against E. coli was further enhanced by immune serum. Cefamandole at 4 x the MBC did not affect the survival of intracellular S. aureus, but killed 41% of extracellular bacteria by 1 h and 99% after 3 h. The data suggest that cefamandole possesses an intracellular antibacterial activity against E. coli that seems at least in part due to a positive cooperation of antibiotic with the O2-independent microbicidal system of macrophages.

Name

Type

Language

CEFAMANDOLE

Official Name

English

J01DC03

Preferred Name

English

cefamandole [INN]

Common Name

English

COMPOUND-83405

Code

English

7-D-MANDELAMIDO-3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-3-CEPHEM-4-CARBOXYLIC ACID

Common Name

English

CEPHAMANDOLE

Common Name

English

CEFAMANDOLE [MI]

Common Name

English

5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7-((HYDROXYPHENYLACETYL)AMINO)-3-(((1-METHYL-1H-TETRAZOL-5-YL)THIO)METHYL)-8-OXO-, (6R-(6.ALPHA.,7.BETA.(R*)))-

Common Name

English

CEFAMANDOLE [VANDF]

Common Name

English

CEFAMANDOLE [USAN]

Common Name

English

(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

Common Name

English

CEFAMANDOLE [MART.]

Common Name

English

COMPOUND 83405

Code

English

Cefamandole [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01DC03