U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C8H10N2S
Molecular Weight 166.2448
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETHIONAMIDE

SMILES

CCc1cc(ccn1)C(=N)S

InChI

InChIKey=AEOCXXJPGCBFJA-UHFFFAOYSA-N
InChI=1S/C8H10N2S/c1-2-7-5-6(8(9)11)3-4-10-7/h3-5H,2H2,1H3,(H2,9,11)

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created using several sources including: http://www.ncbi.nlm.nih.gov/pubmed/13741471; https://www.ncbi.nlm.nih.gov/pubmed/17220416; http://www.ncbi.nlm.nih.gov/pubmed/26435990

Ethionamide is a second-line agent, structurally similar to isoniazid, used as a second-line therapy for the treatment of multidrug-resistant tuberculosis or active tuberculosis in case of patient intolerance to other drugs. Depending on its the concentration at the infected site and the susceptibility of the infecting organism it may be bacteriostatic or bactericidal. When used alone rapidly develops bacterial resistance. Ethionamide was approved by FDA in 1965 as TRECATOR manufactured by Wyeth Pharmaceuticals Inc. (purchased by Pfizer in 2009). Ethionamide is specific for Mycobacteria and is thought to exert a toxic effect on mycolic acid components of the bacterial cell wall when activated through intermediate S-oxidation by EtaA. Mycolic acid synthesis was shown to be inhibited by ethionamide in the EthA protein-overexpressing mycobacteria,

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P9WIE5|||Q50553
Gene ID: 885638.0
Gene Symbol: katG
Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
TRECATOR

Approved Use

Trecator is primarily indicated for the treatment of active tuberculosis in patients with M. tuberculosis resistant to isoniazid or rifampin, or when there is intolerance on the part of the patient to other drugs. Its use alone in the treatment of tuberculosis results in the rapid development of resistance. It is essential, therefore, to give a suitable companion drug or drugs, the choice being based on the results of susceptibility tests. If the susceptibility tests indicate that the patient's organism is resistant to one of the first-line antituberculosis drugs (i.e., isoniazid or rifampin) yet susceptible to ethionamide, ethionamide should be accompanied by at least one drug to which the M. tuberculosis isolate is known to be susceptible.3 If the tuberculosis is resistant to both isoniazid and rifampin, yet susceptible to ethionamide, ethionamide should be accompanied by at least two other drugs to which the M. tuberculosis isolate is known to be susceptible.3 Patient nonadherence to prescribed treatment can result in treatment failure and in the development of drug-resistant tuberculosis, which can be life-threatening and lead to other serious health risks. It is, therefore, essential that patients adhere to the drug regimen for the full duration of treatment. Directly observed therapy is recommended for all patients receiving treatment for tuberculosis. Patients in whom drug-resistant M. tuberculosis organisms are isolated should be managed in consultation with an expert in the treatment of drug-resistant tuberculosis.

Launch Date

-1.47484803E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.16 μg/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHIONAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7.67 μg × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHIONAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.92 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHIONAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
70%
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHIONAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.1 g 2 times / week multiple, oral
MTD
Dose: 0.1 g, 2 times / week
Route: oral
Route: multiple
Dose: 0.1 g, 2 times / week
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
0.5 g 2 times / week multiple, oral
MTD
Dose: 0.5 g, 2 times / week
Route: oral
Route: multiple
Dose: 0.5 g, 2 times / week
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
0.75 g 2 times / week multiple, oral
MTD
Dose: 0.75 g, 2 times / week
Route: oral
Route: multiple
Dose: 0.75 g, 2 times / week
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
1.25 g 2 times / week multiple, oral
MTD
Dose: 1.25 g, 2 times / week
Route: oral
Route: multiple
Dose: 1.25 g, 2 times / week
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
1.5 g 2 times / week multiple, oral
MTD
Dose: 1.5 g, 2 times / week
Route: oral
Route: multiple
Dose: 1.5 g, 2 times / week
Co-administed with::
AMINOSALICYLATE SODIUM(6 g; oral; 2/week)
ISONIAZID(15 mg/kg; oral; 2/week)
Sources:
unhealthy, >12
n = 27
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: >12
Sex: M+F
Population Size: 27
Sources:
PubMed

PubMed

TitleDatePubMed
The antituberculous activity of thioamide in vitro and in the experimental animal (mouse and guinea pig).
1960 May
Mycolic acid synthesis: a target for ethionamide in mycobacteria?
1992 Jun
Conformational analysis of thiopeptides: free energy calculations on the effects of thio-substitutions on the conformational distributions of alanine dipeptides.
2001
[Components of monitoring drug resistance of tuberculosis agent in the evaluation of effectiveness of the national tuberculosis control program].
2001
Synthesis of 3'-thioamido-modified 3'-deoxythymidine-5'-triphosphates and their use as chain terminators in Sanger-DNA sequencing.
2001 Apr-Jul
[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].
2001 Dec
Synthesis, X-ray crystallographic structures of thio substituted N-acetyl N'-methylamide alanine and evaluation of sp sulfur parameters of the CFF91 force field.
2001 Jul
Solvent effects on the thioamide rotational barrier: an experimental and theoretical study.
2001 Mar 7
Compatibility of the thioamide functional group with beta-sheet secondary structure: incorporation of a thioamide linkage into a beta-hairpin peptide.
2001 Oct 18
Population pharmacokinetics of ethionamide in patients with tuberculosis.
2002
Comparative study on the use of solid media: Löwenstein-Jensen and Ogawa in the determination of anti-tuberculosis drug susceptibility.
2002
Long-term follow up of childhood tuberculous meningitis.
2002 Aug
2-Pyridinethiol/2-pyridinethione tautomeric equilibrium. A comparative experimental and computational study.
2002 Dec 13
Conformational stability of helical peptides containing a thioamide linkage.
2002 Dec 26
High-pressure Fourier transform micro-Raman spectroscopic investigation of diiodine-heterocyclic thioamide adducts.
2002 Oct
Diversity in the oxidation of substrates by cytochrome P450 2D6: lack of an obligatory role of aspartate 301-substrate electrostatic bonding.
2002 Sep 10
Reaction and characterization of thioamide dianions derived from N-benzyl thioamides.
2003 Oct 31
Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system.
2003 Sep
Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.
2004
Pharmacy data for tuberculosis surveillance and assessment of patient management.
2004 Aug
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase.
2004 Jan 30
Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.
2004 Jun
Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.
2004 Jun
Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities.
2004 Nov
Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient.
2004 Oct
Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria.
2005 Feb
Analysis of Mycobacterium tuberculosis isolates from treatment failure patients living in East Timor.
2005 Jan
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: If patient exhibits poor gastrointestinal tolerance, TRECATOR has to be administered in divided doses, with a maximum daily dosage of 1 gram
15 to 20 mg/kg/day, administered once daily
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Standardized in vitro susceptibility method for testing ethionamide against M. tuberculosis organisms: after 2 to 3 weeks of incubation, MIC99 values are calculated.
Two standardized in vitro susceptibility methods are available for testing ethionamide against M. tuberculosis organisms. The modified proportion method (CDC or NCCLS M24-P) utilizes Middlebrook and Cohn 7H10 agar medium impregnated with ethionamide at a final concentration of 5.0 ug/mL. After 2 to 3 weeks of incubation, MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug, of at least 1% of the growth in the control culture, indicates resistance.
Name Type Language
ETHIONAMIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN   USAN  
Official Name English
ETHIONAMIDE [VANDF]
Common Name English
ETHIONAMIDE [INN]
Common Name English
ETHIONAMIDE [HSDB]
Common Name English
ETHIONAMIDE [IARC]
Common Name English
ETHIONAMIDE [MI]
Common Name English
ETHIONAMIDE [EP MONOGRAPH]
Common Name English
ETHIONAMIDE [ORANGE BOOK]
Common Name English
TRECATOR
Brand Name English
ETHIONAMIDE [USAN]
Common Name English
1314-TH
Code English
TRECATOR-SC
Brand Name English
4-PYRIDINECARBOTHIOAMIDE, 2-ETHYL-
Systematic Name English
1314 TH
Code English
ETHIONAMIDE [USP MONOGRAPH]
Common Name English
ETHIONAMIDUM [WHO-IP LATIN]
Common Name English
BAYER 5312
Code English
2-ETHYLTHIOISONICOTINAMIDE
Systematic Name English
ETHIONAMIDE [USP-RS]
Common Name English
ETHIONAMIDE [MART.]
Common Name English
ETHIONAMIDE [WHO-IP]
Common Name English
NSC-255115
Code English
ETHIONAMIDE [WHO-DD]
Common Name English
NIZOTIN
Common Name English
Classification Tree Code System Code
WHO-VATC QJ04AD03
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WHO-ESSENTIAL MEDICINES LIST 6.2.4
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LIVERTOX 383
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NDF-RT N0000175483
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NCI_THESAURUS C280
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WHO-ATC J04AD03
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Code System Code Type Description
FDA UNII
OAY8ORS3CQ
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PRIMARY
EPA CompTox
536-33-4
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PRIMARY
ChEMBL
CHEMBL1441
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PRIMARY
LACTMED
Ethionamide
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PRIMARY
MESH
D005000
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PRIMARY
DRUG BANK
DB00609
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PRIMARY
EVMPD
SUB07278MIG
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PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
ETHIONAMIDE
Created by admin on Fri Jun 25 20:52:10 UTC 2021 , Edited by admin on Fri Jun 25 20:52:10 UTC 2021
PRIMARY Description: Small yellow crystals or a yellow, crystalline powder; odour, slight.Solubility: Practically insoluble in water; soluble in methanol R; sparingly soluble in ethanol (~750 g/l) TS; slightly soluble in ether R.Category: Antileprosy drug.Storage: Ethionamide should be kept in a tightly closed container.Additional information: Ethionamide darkens on exposure to light.Definition: Ethionamide contains not less than 98.0% and not more than 101.0% of C8H10N2S, calculated with reference to the dried substance.
USP_CATALOG
1261004
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PRIMARY USP-RS
CAS
536-33-4
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PRIMARY
DRUG CENTRAL
1083
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PRIMARY
PUBCHEM
2761171
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PRIMARY
NCI_THESAURUS
C47522
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PRIMARY
MERCK INDEX
M5061
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PRIMARY Merck Index
WIKIPEDIA
ETHIONAMIDE
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PRIMARY
HSDB
7473
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PRIMARY
ECHA (EC/EINECS)
208-628-9
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PRIMARY
INN
867
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PRIMARY
RXCUI
4127
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PRIMARY RxNorm