CEFAMANDOLE SODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H17N6O5S2.Na
Molecular Weight	484.485
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[C@H]2NC(=O)[C@H](O)C4=CC=CC=C4)C([O-])=O

InChI

InChIKey=OJMNTWPPFNMOCJ-CFOLLTDRSA-M

InChI=1S/C18H18N6O5S2.Na/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);/q;+1/p-1/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 233 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3266730	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Lower respiratory infections 3 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	MANDOL Approved Use Unknown Launch Date 1978
Urinary tract infections 205 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	MANDOL Approved Use Unknown Launch Date 1978
Peritonitis 22 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	MANDOL Approved Use Unknown Launch Date 1978
Sepsis 71 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	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 n = 2 Health Status: unhealthy Age Group: 43 - 58 years Sex: F Population Size: 2 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 n = 20 Health Status: unhealthy Sex: F Population Size: 20 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 n = 24 Health Status: unhealthy Condition: renal impairment Sex: M Population Size: 24 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 n = 2 Health Status: unhealthy Age Group: 43 - 58 years Sex: F Population Size: 2 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 n = 20 Health Status: unhealthy Sex: F Population Size: 20 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 n = 20 Health Status: unhealthy Sex: F Population Size: 20 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 n = 20 Health Status: unhealthy Sex: F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/7405988/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 146 OAT1 599 OAT2 145 OAT3 642

Drug as perpetrator

Target	Modality	Activity
OAT2 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1570 uM]
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1140 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 30 uM]
OAT3 644	inhibitor 3277 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
In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria.	1988 Dec	3243734
Review of the use of cephalosporins in children with anaphylactic reactions from penicillins.	2002 Jul	18159398
[Beta-lactam resistance in aquatic Enterobacter cloacae strains using phenotypic and genotypic criteria].	2002 Jul-Dec	15085610
Antibiotic resistance patterns of group B streptococcal clinical isolates.	2004	15460188
Vibrio vulnificus in Taiwan.	2004 Aug	15496235
Cross-reactivity and tolerability of cephalosporins in patients with immediate hypersensitivity to penicillins.	2004 Jul 6	15238366
Polyurethanes loaded with antibiotics: influence of polymer-antibiotic interactions on in vitro activity against Staphylococcus epidermidis.	2004 Oct	15565910
Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.	2004 Sep 14	15342186
Voltammetric analysis of Cu (II), Cd (II) and Zn (II) complexes and their cyclic voltammetry with several cephalosporin antibiotics.	2005 Feb	15713559
Acute ST-segment elevation myocardial infarction after amoxycillin-induced anaphylactic shock in a young adult with normal coronary arteries: a case report.	2005 Feb 25	15733315
Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.	2005 Jan	15567297
Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis clinical isolates from orthopaedic implant infections.	2005 Nov	15949842
Systemic and local antibiotic prophylaxis in the prevention of Staphylococcus epidermidis graft infection.	2005 Oct 21	16242027
IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient.	2006 Dec	17176412
Case report: infective endocarditis caused by Brevundimonas vesicularis.	2006 Dec 29	17194310
Ameba-associated microorganisms and diagnosis of nosocomial pneumonia.	2006 Feb	16494750
Nosocomial bloodstream infections caused by Klebsiella pneumoniae: impact of extended-spectrum beta-lactamase (ESBL) production on clinical outcome in a hospital with high ESBL prevalence.	2006 Feb 14	16478537
[Reversion of antibiotic-sensitivity of lactic acid bacteria in grafted cultures of lymphoblastoid human cells].	2006 Nov-Dec	17243366
Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses.	2006 Oct	16941232
Antimicrobial therapy for acute cholangitis: Tokyo Guidelines.	2007	17252298
Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift.	2007 Mar	17349459
Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report.	2007 Mar 2	17331261
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
Semiparametric mixed-effects analysis of PK/PD models using differential equations.	2008 Aug	18781382
Should we change antibiotic prophylaxis for lung surgery? Postoperative pneumonia is the critical issue.	2008 Dec	19021965
Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics.	2008 Jun	18339814
The occurrence of osteoarthritis at a minimum of ten years after reconstruction of the anterior cruciate ligament.	2008 Jun 10	18544170
Spectrophotometeric Determination of Cefuroxime Axetil from bulk and in its tablet dosage form.	2008 Mar-Apr	20046725
Efficacy of collagen silver-coated polyester and rifampin-soaked vascular grafts to resist infection from MRSA and Escherichia coli in a dog model.	2008 Nov	18835516
Determination of cephalosporins in solid binary mixtures by polarized IR- and Raman spectroscopy.	2008 Sep 10	18602240
Rapid nanoparticle-mediated monitoring of bacterial metabolic activity and assessment of antimicrobial susceptibility in blood with magnetic relaxation.	2008 Sep 23	18810269
Translocation of bacterial NOD2 agonist and its link with inflammation.	2009	19638210
Suspected anaphylactic reactions associated with anaesthesia.	2009 Feb	19143700
A case of multidrug-resistant Salmonella enterica serovar Typhi treated with a bench to bedside approach.	2009 Feb 28	19259362
Detection of Extended Spectrum β-lactamase Production Among Uropathogens.	2009 Jan	21938241
Prevalence and molecular characterization of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in Riyadh, Saudi Arabia.	2009 Jul-Aug	19587523
Data correction pre-processing for electronically stored blood culture results: implications on microbial spectrum and empiric antibiotic therapy.	2009 Jun 7	19500418
Antibiotic delivery polyurethanes containing albumin and polyallylamine nanoparticles.	2009 Mar 2	19136061
Antibiotic prophylaxis for lung surgery: bronchial colonization is the critical issue?	2009 Sep	19699971
Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation.	2010	20385017
Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria.	2010 Apr	20186407
Single-dose versus multiple-dose antibiotic prophylaxis for the surgical treatment of closed fractures.	2010 Apr	20148647
Sequencing and genetic variation of multidrug resistance plasmids in Klebsiella pneumoniae.	2010 Apr 12	20405037
Selective decontamination of the gastrointestinal tract in patients undergoing esophageal resection.	2010 Dec 16	21162752
Prevalence and risk factors for extended spectrum Beta-lactamase-producing uropathogens in patients with urinary tract infection.	2010 Jul	20664784
Impact of the RNA chaperone Hfq on multidrug resistance in Escherichia coli.	2010 May	20211861
Differentiation between probiotic and wild-type Bacillus cereus isolates by antibiotic susceptibility test and Fourier transform infrared spectroscopy (FT-IR).	2010 May 30	20303194
Structures of the Michaelis complex (1.2 Å) and the covalent acyl intermediate (2.0 Å) of cefamandole bound in the active sites of the Mycobacterium tuberculosis β-lactamase K73A and E166A mutants.	2010 Nov 16	20961112
Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.	2010 Sep 30	20941353

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 SODIUM

Common Name

English

Monosodium (6R,7R)-7-(R)-mandelamido-3-[[(1-methyl-1-H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

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-(6A,7B(R*)))-, MONOSODIUM SALT

Common Name

English

NSC-758169

Code

English

Cefamandole sodium [WHO-DD]

Common Name

English

CEFAMANDOLE SODIUM [MART.]

Common Name

English

CEFAMANDOLE SODIUM [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C357