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 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 2.75702415E11
Urinary tract infections 205 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Peritonitis 22 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Sepsis 71 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8429	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 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
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
Acute tubular necrosis following high-dose cefamandole therapy for Hemophilus parainfluenzae endocarditis.	1981 May-Jun	7246598
The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.	1995 Apr	7624446
Determination of unbound cefamandole in rat blood by microdialysis and microbore liquid chromatography.	2001 Feb	11180295
Antibiotic prophylaxis in orthopedic prosthetic surgery.	2001 Nov	11936379
Cephalosporins in surgical prophylaxis.	2001 Nov	11936371
Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.	2002 Jul	12096009
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
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.	2002 Mar	12118443
Interaction of human organic anion transporters with various cephalosporin antibiotics.	2002 Mar 8	11909604
beta-Lactam allergenic determinants: fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin.	2002 Nov	12569987
Comparison of screening methods for TEM- and SHV-derived extended-spectrum beta-lactamase detection.	2002 Nov	12445009
Formation of Propionibacterium acnes biofilms on orthopaedic biomaterials and their susceptibility to antimicrobials.	2003 Aug	12763449
Antibiotic resistance patterns of group B streptococcal clinical isolates.	2004	15460188
Vibrio vulnificus in Taiwan.	2004 Aug	15496235
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
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
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
Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses.	2006 Oct	16941232
Antimicrobial therapy for acute cholangitis: Tokyo Guidelines.	2007	17252298
Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis.	2007 Mar	17321857
New active site oriented glyoxyl-agarose derivatives of Escherichia coli penicillin G acylase.	2007 Sep 10	17845725
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
The occurrence of osteoarthritis at a minimum of ten years after reconstruction of the anterior cruciate ligament.	2008 Jun 10	18544170
Determination of cephalosporins in solid binary mixtures by polarized IR- and Raman spectroscopy.	2008 Sep 10	18602240
Detection of Extended Spectrum β-lactamase Production Among Uropathogens.	2009 Jan	21938241
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
Sequencing and genetic variation of multidrug resistance plasmids in Klebsiella pneumoniae.	2010 Apr 12	20405037
Prevalence and risk factors for extended spectrum Beta-lactamase-producing uropathogens in patients with urinary tract infection.	2010 Jul	20664784
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

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 `Sat Dec 16 15:51:10 UTC 2023` Edited by `admin` on `Sat Dec 16 15:51:10 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