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

[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=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

Molecular Formula	C18H18N6O5S2
Molecular Weight	462.503
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 232 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3266730	Inhibitor 8228

Conditions

Condition	Modality	Highest Phase	Product
Lower respiratory infections 3 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8360	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Urinary tract infections 204 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8360	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Peritonitis 22 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8360	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Sepsis 71 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8360	MANDOL Approved Use Unknown Launch Date 2.75702415E11

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 145 OAT1 595 OAT2 144 OAT3 636

Drug as perpetrator

Target	Modality	Activity
OAT2 146	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1570 uM]
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1140 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 30 uM]
OAT3 638	inhibitor 3240 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
Comparative incidence of phlebitis due to buffered cephalothin, cephapirin, and cefamandole.	1976 Apr	5053
Comparison of thrombophlebitis associated with three cephalosporin antibiotics.	1976 Sep	791101
[Experimental studies in animals on the nephrotoxicity of some new cephalosporin antibiotics: cefamandole, EMD 29 645, and 29 946 (author's transl)].	1980	7190410
Cefamandole for treatment of obstetrical and gynecological infections.	1980	7010540
Acute tubular necrosis following high-dose cefamandole therapy for Hemophilus parainfluenzae endocarditis.	1981 May-Jun	7246598
Empiric therapy for infections in patients with granulocytopenia. Continuous v interrupted infusion of tobramycin plus cefamandole.	1984 May	6712393
Extravascular hemolysis following the administration of cefamandole.	1985 Feb	3970014
Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods.	1985 Jan	3920957
Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex.	1987	3428133
In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria.	1988 Dec	3243734
Acute renal failure due to cephamandole.	1988 Feb 6	3125941
The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.	1995 Apr	7624446
Review of the use of cephalosporins in children with anaphylactic reactions from penicillins.	2002 Jul	18159398
Antimicrobial therapy for acute cholangitis: Tokyo Guidelines.	2007	17252298
[Primary peritonitis in Sub-Saharian Africa: a 15 case series].	2007 Apr	17691434
Enzymatic synthesis of cephalosporins. The immobilized acylase from Arthrobacter viscosus: a new useful biocatalyst.	2007 Dec	17879093
Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift.	2007 Mar	17349459
Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis.	2007 Mar	17321857
Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report.	2007 Mar 2	17331261
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
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.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 21:23:33 UTC 2023` Edited by `admin` on `Thu Jul 06 21:23:33 UTC 2023`
Record UNII	5CKP8C2LLI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CEFAMANDOLE

Official 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

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

J01DC03

Code

English

COMPOUND 83405

Code

English

Cefamandole [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01DC03