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

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H24N2O2
Molecular Weight 204.3102
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETHAMBUTOL

SMILES

CC[C@@]([H])(CO)NCCN[C@@]([H])(CC)CO

InChI

InChIKey=AEUTYOVWOVBAKS-UWVGGRQHSA-N
InChI=1S/C10H24N2O2/c1-3-9(7-13)11-5-6-12-10(4-2)8-14/h9-14H,3-8H2,1-2H3/t9-,10-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.drugbank.ca/drugs/DB00330

ETHAMBUTOL HYDROCHLORIDE is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. Ethambutol inhibits RNA synthesis and decreases tubercle bacilli replication. Nearly all strains of M. tuberculosis and M. kansasii as well as a number of strains of MAC are sensitive to ethambutol. Ethambutol inhibits arabinosyl transferases which is involved in cell wall biosynthesis. By inhibiting this enzyme, the bacterial cell wall complex production is inhibited. This leads to an increase in cell wall permeability. ETHAMBUTOL HCl is indicated for the treatment of pulmonary tuberculosis. It should not be used as the sole antituberculous drug, but should be used in conjunction with at least one other antituberculous drug.

CNS Activity

Curator's Comment:: Ethambutol penetrated the CSF in very few normal subjects; but in patients with meningitis the mean levels were 0.48 μg/ml at 3 hours, 0.35 μg/ml at 6 hours, 0.12 μg/ml at 9 hours, 0.18 μg/ml at 12 hours and 0.07 μg/ml at 15 hours and 24 hours.

Originator

Curator's Comment:: Wilkinson and coworkers from Lederle laboratories first reported the synthesis and activity of ethambutol (EMB) in 1961.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Probable arabinosyltransferase C
Target ID: Probable arabinosyltransferase B
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MYAMBUTOL

Approved Use

pulmonary tuberculosis

Launch Date

-6.7996799E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.3 μg/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: aluminum-magnesium antacid
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.5 μg/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.8 μg/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
27.5 μg × h/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered: aluminum-magnesium antacid
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
28 μg × h/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
29.6 μg × h/mL
25 mg/kg single, oral
dose: 25 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ETHAMBUTOL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
Doses

Doses

DosePopulationAdverse events​
25 mg/kg 1 times / day multiple, oral
Recommended
Dose: 25 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg/kg, 1 times / day
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: 79 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Agranulocytosis...
AEs leading to
discontinuation/dose reduction:
Agranulocytosis (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Agranulocytosis 1 patient
Disc. AE
25 mg/kg 1 times / day multiple, oral
Recommended
Dose: 25 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg/kg, 1 times / day
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: pulmonary tuberculosis
Age Group: 79 years
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [IC50 53.9 uM]
likely
Comment: Drug-drug interaction index prediction
Page: 1.0
moderate [IC50 57.6 uM]
likely
Comment: Drug-drug interaction index prediction
Page: 1.0
moderate [IC50 8.4 uM]
moderate [IC50 9.4 uM]
no
no
no
no
no
no
no
no
no
no
unlikely
Comment: Drug-drug interaction index prediction
Page: 1.0
strong [IC50 253.8 uM]
likely
Comment: Drug-drug interaction index prediction
Page: 1.0
strong [IC50 92.6 uM]
likely
Comment: Drug-drug interaction index prediction
Page: 1.0
strong [Ki 1.4 uM]
strong [Ki 2.9 uM]
weak [IC50 4100 uM]
likely
Comment: Drug-drug interaction index prediction
Page: 1.0
weak
weak
weak
weak
weak
weak
yes [IC50 88.2 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
[New aspects of tuberculosis therapy].
1975 Feb 22
Ocular toxicity with ethambutol in tuberculosis patients.
1976 Jul
[Treatment of severe optic neuritis caused by ethambutol].
1976 Nov
In vivo activities of newer rifamycin analogs against Mycobacterium avium infection.
1991 Oct
Chlorpromazine: a drug potentially useful for treating mycobacterial infections.
1992
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?
1992 Dec
CI-960 (PD127391 or AM-1091), sparfloxacin, WIN 57273, and isepamicin activity against clinical isolates of Mycobacterium avium-intracellularae complex, M. chelonae, and M. fortuitum.
1992 Feb
Activities of eighteen antimicrobial regimens against Mycobacterium avium infection in beige mice.
1999 Fall
Ethambutol-induced psychosis: a case report.
1999 Oct
A new class of antituberculosis agents.
2000 Aug 24
Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs.
2000 Feb 1
Synthesis and in vitro anti-mycobacterium activity of N-alkyl-1, 2-dihydro-2-thioxo-3-pyridinecarbothioamides. Preliminary toxicity and pharmacokinetic evaluation.
2000 Jan 27
Minimal change nephrotic syndrome associated with rifampicin treatment.
2000 Jul
Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors.
2000 Sep
Liver function tests in patients of pulmonary tuberculosis using four different drug regimens.
2001 Apr-Jun
Use of a recombinant strain of Mycobacterium avium expressing beta-galactosidase to evaluate the activities of antimycobacterial agents inside macrophages.
2001 Jan
Activity of moxifloxacin by itself and in combination with ethambutol, rifabutin, and azithromycin in vitro and in vivo against Mycobacterium avium.
2001 Jan
Antimycobacterial plant terpenoids.
2001 Nov
Optic neuropathy after treatment with anti-tuberculous drugs in a subject with Leber's hereditary optic neuropathy mutation.
2001 Sep
Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis.
2002 Aug
Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta.
2003 Apr
Trends in the use of antituberculosis drugs in Spain 1993-1998.
2003 Apr-May
Antimycobacterial activity of diospyrin derivatives and a structural analogue of diospyrin against Mycobacterium tuberculosis in vitro.
2003 Feb
Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy.
2003 Jan
Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to macrolide-containing regimens for treatment of Mycobacterium avium disease.
2003 Jun 15
Ethambutol-induced optic neuropathy in a patient with pituitary macroadenoma: case report.
2003 Nov-Dec
[Unusual therapeutic approach in treatment of pulmonary tuberculosis in six year old girl].
2004
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
Ethambutol-induced acute renal failure.
2004 May
[Septic shock following intracavitary Bacillus Calmette-Guerin therapy for postcystectomy ureteral cancer].
2004 Sep
[Mycobacterium bovis tuberculosis in a female patient with AIDS].
2005 Apr-Jun
Multifocal ERG in ethambutol associated visual loss.
2005 Aug
Rapidly developing optic neuritis secondary to ethambutol: possible mechanism of injury.
2005 Jul
Multifocal electroretinogram demonstrated macular toxicity associated with ethambutol related optic neuropathy.
2005 Jun
Antimycobacterial agents differ with respect to their bacteriostatic versus bactericidal activities in relation to time of exposure, mycobacterial growth phase, and their use in combination.
2005 Jun
Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy.
2005 May
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes.
2005 Sep 19
Menstrual disorders in nongenital tuberculosis.
2006
[Case of SIADH caused by ethionamide in a patient with pulmonary tuberculosis].
2006 Dec
[Ocular toxicity by the use of ethambutol].
2006 Jul-Aug
Activity of 7-methyljuglone in combination with antituberculous drugs against Mycobacterium tuberculosis.
2006 Nov
Abnormal multifocal electroretinogram (mfERG) in ethambutol toxicity.
2006 Oct-Dec
Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy.
2007 Jul
Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct mycobacteria growth indicator tube and phage amplified biological assay compared to BACTEC 460 TB.
2007 Mar
Patents

Sample Use Guides

Usual Adult Dose for Tuberculosis - Active Initial treatment: 15 mg/kg orally once a day for 6 to 8 weeks with concurrent isoniazid therapy. Retreatment: 25 mg/kg orally once a day for 60 days concurrently with at least one other anti-TB drug. After 60 days, decrease dose to 15 mg/kg orally once a day. As an alternative to single daily dose, a dose of 40 mg/kg orally twice a week or 30 mg/kg orally 3 times a week can be administered. This generally follows 2 weeks of daily therapy.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: In vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv was evaluated.
The antimycobacterial activity of ethambutol was assessed against Mycobacterium tuberculosis (H37Rv) strain using micro plate Alamar Blue assay (MABA). Compound showed inhibitory activity with MIC value 3.125 ug/mL
Name Type Language
ETHAMBUTOL
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
(2S,2S)-2,2-(ETHANE-1,2-DIYLDIIMINO)DIBUTAN-1-OL
Systematic Name English
ETHAMBUTOL [VANDF]
Common Name English
ETHAMBUTOL [HSDB]
Common Name English
ETHAMBUTOL [INN]
Common Name English
ETHAMBUTOL [WHO-DD]
Common Name English
ETHAMBUTOL [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC J04AM07
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-VATC QJ04AM03
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ATC J04AK02
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-VATC QJ04AK02
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.4
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ETH/ISO)
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ATC J04AM03
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-VATC QJ04AM06
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ATC J04AM06
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ETH/ISO/RIF)
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ETH/ISO/PYR/RIF)
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
NDF-RT N0000175483
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
NCI_THESAURUS C280
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
LIVERTOX 381
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C61755
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
MERCK INDEX
M5045
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY Merck Index
DRUG CENTRAL
1073
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-810-6
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL44884
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
FDA UNII
8G167061QZ
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
LACTMED
Ethambutol
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
CAS
74-55-5
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
EPA CompTox
74-55-5
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
MESH
D004977
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
HSDB
3078
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
EVMPD
SUB07271MIG
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
RXCUI
4110
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
ETHAMBUTOL
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
DRUG BANK
DB00330
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
INN
1074
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY
PUBCHEM
14052
Created by admin on Sat Jun 26 16:34:25 UTC 2021 , Edited by admin on Sat Jun 26 16:34:25 UTC 2021
PRIMARY