CEFOTIAM HEXETIL HYDROCHLORIDE

Details

Stereochemistry	EPIMERIC
Molecular Formula	C27H37N9O7S3.2ClH
Molecular Weight	768.756
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of CEFOTIAM HEXETIL HYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.[H][C@]12SCC(CSC3=NN=NN3CCN(C)C)=C(N1C(=O)[C@H]2NC(=O)CC4=CSC(N)=N4)C(=O)OC(C)OC(=O)OC5CCCCC5

InChI

InChIKey=FFSANQNELHESQJ-LWBICVDYSA-N

InChI=1S/C27H37N9O7S3.2ClH/c1-15(42-27(40)43-18-7-5-4-6-8-18)41-24(39)21-16(13-46-26-31-32-33-35(26)10-9-34(2)3)12-44-23-20(22(38)36(21)23)30-19(37)11-17-14-45-25(28)29-17;;/h14-15,18,20,23H,4-13H2,1-3H3,(H2,28,29)(H,30,37);2*1H/t15?,20-,23-;;/m1../s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00229
Curator's Comment: Description was created based on several sources, including

Cefotiam is a third generation beta-lactam cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. The bactericidal activity of cefotiam results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Penicillin-binding protein 1A 45 Target ID: CHEMBL1813 Sources: https://www.ncbi.nlm.nih.gov/pubmed/371539	Binding Agent 1064
Penicillin-binding protein 1B 22 Target ID: CHEMBL1814 Sources: https://www.ncbi.nlm.nih.gov/pubmed/371539	Binding Agent 1064
Penicillin-binding protein 2 24 Target ID: CHEMBL1840 Sources: https://www.ncbi.nlm.nih.gov/pubmed/371539	Binding Agent 1064
Bacterial penicillin-binding protein 233 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/379387	Inhibitor 8297
Escherichia coli 82 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15535040	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cystitis 27 Sources: http://www.mims.com/india/drug/info/cefotiam?type=full&mtype=generic#Indications	Curative		Approved 8429	CEFOTIAM Approved Use Parenteral Prophylaxis for surgical infection, Postoperative infections, Bacterial septicaemia, Bone and joint infections, Cholangitis, Cholecystitis, Peritonitis, Prostatitis, Pyelonephritis, Respiratory tract infections, Skin and soft tissue infections, Infections caused by susceptible organisms, Cystitis, Urethritis Launch Date 1987
Respiratory tract infections 85 Sources: http://www.mims.com/india/drug/info/cefotiam?type=full&mtype=generic#Indications	Curative		Approved 8429	CEFOTIAM Approved Use Parenteral Prophylaxis for surgical infection, Postoperative infections, Bacterial septicaemia, Bone and joint infections, Cholangitis, Cholecystitis, Peritonitis, Prostatitis, Pyelonephritis, Respiratory tract infections, Skin and soft tissue infections, Infections caused by susceptible organisms, Cystitis, Urethritis Launch Date 1987

C_max

Value	Dose	Co-administered	Analyte	Population
124.6 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9266270	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOTIAM serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.8 mg/kg EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9266270	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOTIAM unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
171.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9266270	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOTIAM serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9266270	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOTIAM serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9266270	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:		CEFOTIAM unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g 1 times / day multiple, intramuscular Studied dose Dose: 2 g, 1 times / day Route: intramuscular Route: multiple Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6287388	unhealthy, 23 - 76 years n = 30 Health Status: unhealthy Condition: urinary tract infections Age Group: 23 - 76 years Sex: M+F Population Size: 30 Sources: https://pubmed.ncbi.nlm.nih.gov/6287388	Sources: https://pubmed.ncbi.nlm.nih.gov/6287388
7 g 1 times / day multiple, intravenous Studied dose Dose: 7 g, 1 times / day Route: intravenous Route: multiple Dose: 7 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6325736	unhealthy, adult n = 26 Health Status: unhealthy Condition: chronic sinusitis \| otitis media Age Group: adult Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/6325736	Sources: https://pubmed.ncbi.nlm.nih.gov/6325736
200 mg/kg 1 times / day multiple, intravenous Studied dose Dose: 200 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6270413	unhealthy, children n = 26 Health Status: unhealthy Age Group: children Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/6270413	Sources: https://pubmed.ncbi.nlm.nih.gov/6270413

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16098483/	yes [IC50 212.6 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16098483/	yes [IC50 639.7 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:355510	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:355510
ChemicalBook	CB7367629	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7367629
ZINC	ZINC000003830445	http://zinc15.docking.org/substances/ZINC000003830445
eMolecules	31229753	https://www.emolecules.com/cgi-bin/more?vid=31229753

PubMed

Title	Date	PubMed
Renal function in surgical patients after administration of low-flow sevoflurane and amikacin.	2002	14566491
[A questionnaire survey on antimicrobial chemotherapy for acute peritonitis].	2002 Dec	12621738
[Antibacterial activities of fosfomycin against several fresh clinical isolates--comparison of the test methods for antibacterial activity].	2002 Dec	12621737
[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)].	2002 Oct	12532637
[A questionnaire survey on the theory of postoperative infection prophylaxis in urology].	2002 Oct	12532634
[beta-lactamase-producing activity and antimicrobial susceptibility of major pathogenic bacteria isolated from clinical samples. Japan beta-lactamase Research Group].	2002 Sep	12599526
Suitability of cefotiam and cefuroxime axetil for the perioperative short-term prophylaxis in tonsillectomy patients.	2003	12642969
[Prophylactic antibiotics in lumbar disc surgery: analysis of 1,030 procedures].	2003	12582943
[Antimicrobial activity of fosfomycin against beta-lactamase-producing methicillin-sensitive Staphylococcus aureus and methicillin-sensitive coagulase-negative staphylococci].	2003 Apr	12825415
Oral antibiotic prophylaxis can influence the inflammatory response in aortic aneurysm repair: results of a randomized clinical study.	2003 Apr	12797394
[Surveillance of susceptibility of clinical isolates to cefmetazole between 2000 and 2002].	2003 Dec	15007873
Enhancement of antimicrobial effects of various antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by combination with fosfomycin.	2003 Dec	14691650
[A questionnaire survey on the theory of postoperative infection prophylaxis in otorhinolaryngology].	2003 Feb	12723395
Successful treatment of a Salmonella aortic arch aneurysm.	2003 Feb	12692933
Natural antibiotic susceptibility of Proteus spp., with special reference to P. mirabilis and P. penneri strains.	2003 Feb	12678409
Protection with antibody to tumor necrosis factor differs with similarly lethal Escherichia coli versus Staphylococcus aureus pneumonia in rats.	2003 Jul	12826846
[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria].	2003 Oct	14692380
[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). I. Susceptibility distribution].	2003 Oct	14692378
Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta-lactam antibiotics in human intestinal cell line Caco-2.	2003 Sep	14567632
Beta-lactamase stability of faropenem.	2003 Sep	14504433
Recovery of the susceptibility of isolated bacterium achieved by giving long-established antibiotics as prophylaxis against postoperative infections.	2004	15338342
[A case of tuberculous pyometrium concurrent with tuberculous pleurisy].	2004 Jan	14999927
Accidental intrathecal infusion of cefotiam: clinical presentation and management.	2004 Jul	15221158
[A case of pulmonary nocardiosis with a polypoid lesion in a bronchus].	2004 Oct	15566003
Flupenthixol and cefotiam: effects on vitamin A metabolism in rats.	2004 Oct	15522128
The significance of the intraoperative repeated dosing of antimicrobials for preventing surgical wound infection in colorectal surgery.	2005	16133667
[Soft tissue infections in oral, maxillofacial, and plastic surgery. Bacterial spectra and antibiotics].	2005 Nov	16228187
[A case of anaphylactic shock due to an antibiotic used preoperatively].	2005 Oct	16231774
Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1.	2005 Oct 1	16098483
Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?	2005 Oct 5	16277717
[Intraocular penetration of cefotiam hydrochloride, a kind of cephalosporin after filtration surgery in rabbit eyes].	2005 Sep	16218433
High frequency oscillatory ventilation and prone positioning in a porcine model of lavage-induced acute lung injury.	2006 Apr 3	16584548
[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). III. Secular changes in susceptibility].	2006 Aug	17111595
Antibiotic prophylaxis in radical prostatectomy: 1-day versus 4-day treatments.	2006 Dec	17118023
Endotoxin shock due to Vibrio vulnificus infection.	2006 Jul-Aug	16935803
Antimicrobial therapy for acute cholangitis: Tokyo Guidelines.	2007	17252298
[Fundamental study on the selection of antimicrobial prophylactic agents in abdominal surgery].	2007 Aug	18018416
In vitro activity of cefotiam against oxacillin-resistant Staphylococcus epidermidis strains--reevaluation of beta-lactam antibiotics efficiency on MRSE.	2007 Jun	17867489
Success of countermeasures against respiratory infection after digestive surgery by strict blood and fluid resuscitation.	2007 Jun	17593504
Randomized prospective comparison of fosfomycin and cefotiam for prevention of postoperative infection following urological surgery.	2007 Oct	17982722
Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia.	2007 Oct	17982717
Bacterial eradication rates with shortened courses of 2nd- and 3rd-generation cephalosporins versus 10 days of penicillin for treatment of group A streptococcal tonsillopharyngitis in adults.	2007 Oct	17908614
Effects of treatment with antimicrobial agents on the human colonic microflora.	2008 Dec	19337440
Long-term intravenous administration of antibiotics for lumbar spinal surgery prolongs the duration of hospital stay and time to normalize body temperature after surgery.	2008 Dec 15	19092628
Spermatic cord abscess with concurrent prostatic abscess involving the seminal vesicle.	2008 Feb	18301983
First outbreak of multidrug-resistant Klebsiella pneumoniae producing both SHV-12-type extended-spectrum beta-lactamase and DHA-1-type AmpC beta-lactamase at a Korean hospital.	2008 Feb 29	18306469
Penetration and exposure of cefotiam into the peritoneal fluid of abdominal surgery patients after intravenous administration.	2008 Jun	18606586
Systemic use of antibiotics does not prevent postoperative infection in elective colorectal surgery: a randomized controlled trial.	2009 Feb	19280298
Investigation of the sensitising and cross-sensitising potential of textile dyes and beta-lactam antibiotics using a biphasic mice local lymph node assay.	2009 Jul	19212757
Rhabdomyolysis developing after transcatheter arterial chemoembolization for hepatocellular carcinoma.	2009 Nov	19680719

Patents

Sample Use Guides

In Vivo Use Guide

Oral Prophylaxis of surgical infections; Susceptible infections Adult: 200-400 mg bid. Parenteral Prophylaxis of surgical infections; Susceptible infections Adult: As hydrochloride: Up to 6 g daily IV/IM in divided doses according to severity of infection. As hexetil hydrochloride: 200-400 mg bid.

Route of Administration: Other

In Vitro Use Guide

In time-kill studies, Cefotiam had high bactericidal activity against Staphylococcus epidermidis strains with low Cefotiam MIC (< or = 2.0 microg/ml), regardless of whether they were mecA positive.

Name

Type

Language

CEFOTIAM HEXETIL HYDROCHLORIDE

Common Name

English

CEFOTIAM 1-(CYCLOHEXYLOXYCARBONYLOXY)ETHYL ESTER DIHYDROCHLORIDE

Common Name

English

5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7-((2-(2-AMINO-4-THIAZOLYL)ACETYL)AMINO)-3-(((1-(2-(DIMETHYLAMINO)ETHYL)-1H-TETRAZOL-5-YL)THIO)METHYL)-8-OXO-, 1-(((CYCLOHEXYLOXY)CARBONYL)OXY)ETHYL ESTER, HYDROCHLORIDE (1:2), (6R,7R)-

Common Name

English

CEFOTIAM HEXETIL DIHYDROCHLORIDE

Common Name

English

CTM-HE HYDROCHLORIDE

Common Name

English

CEFOTIAM HEXETIL HYDROCHLORIDE [JAN]

Common Name

English

CEFOTIAM HEXETIL HCL

Common Name

English

Cefotiam hexetil hydrochloride [WHO-DD]

Common Name

English

CEFOTIAM 1-(CYCLOHEXYLOXYCARBONYLOXY)ETHYL ESTER DIHYDROCHLORIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C357