CEFAMANDOLE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H18N6O5S2
Molecular Weight	462.5056
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cn1c(nnn1)SCC2=C(C(=O)O)N3C(=O)[C@]([H])([C@@]3([H])SC2)N=C([C@@]([H])(c4ccccc4)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 226 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3266730	Inhibitor 7728

Conditions

Condition	Modality	Highest Phase	Product
Lower respiratory infections 3 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8043	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Urinary tract infections 197 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8043	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Peritonitis 22 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8043	MANDOL Approved Use Unknown Launch Date 2.75702415E11
Sepsis 68 Sources: http://www.rxlist.com/mandol-drug/indications-dosage.htm	Curative	Approved 8043	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 131 OAT1 554 OAT2 131 OAT3 588

Drug as perpetrator

Target	Modality	Activity
OAT2 133	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [IC50 1570 uM]
OAT4 131	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 1140 uM]
OAT1 558	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/12650826/	yes [Ki 30 uM]
OAT3 590	inhibitor 3045 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
[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
The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.	1995 Apr	7624446
Occurrence and antibiotic resistance of mesophilic Aeromonas in three riverine freshwaters of Marrakech, Morocco.	2001 Dec 1	12805714
Determination of unbound cefamandole in rat blood by microdialysis and microbore liquid chromatography.	2001 Feb	11180295
Difficulties in the assay of cefamandole highlight the importance of specific methodologies in pharmacokinetic studies.	2001 Jul	11418533
Cephalosporins in surgical prophylaxis.	2001 Nov	11936371
Serotypes, virulence factors, antibiotic sensitivity, beta-lactamase activity and plasmid analysis of Salmonella from children with diarrhea in Tripoli (Libya).	2002	12512253
Systemic and local antibiotic prophylaxis in the prevention of prosthetic vascular graft infection: an experimental study.	2002 Feb	11863329
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
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.	2002 Mar	12118443
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
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
Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.	2005 Jan	15567297
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
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
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
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
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
Suspected anaphylactic reactions associated with anaesthesia.	2009 Feb	19143700
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 prophylaxis for lung surgery: bronchial colonization is the critical issue?	2009 Sep	19699971
Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria.	2010 Apr	20186407
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
Differentiation between probiotic and wild-type Bacillus cereus isolates by antibiotic susceptibility test and Fourier transform infrared spectroscopy (FT-IR).	2010 May 30	20303194

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

CEFAMANDOLE [WHO-DD]

Common 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

Classification Tree Code System Code

WHO-ATC

J01DC03