ETHAMBUTOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H24N2O2
Molecular Weight	204.3098
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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

Molecular Formula	C10H24N2O2
Molecular Weight	204.3098
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Probable arabinosyltransferase C 3 Target ID: Probable arabinosyltransferase C Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297
Probable arabinosyltransferase B 3 Target ID: Probable arabinosyltransferase B Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297
Arabinosyltransferase A 4 Target ID: CHEMBL1877 Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary tuberculosis 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf	Primary		Approved 8429	MYAMBUTOL Approved Use pulmonary tuberculosis Launch Date 1967

C_max

Value	Dose	Co-administered	Analyte	Population
3.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered: aluminum-magnesium antacid	aluminum-magnesium antacid	ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	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

Value	Dose	Co-administered	Analyte	Population
27.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered: aluminum-magnesium antacid	aluminum-magnesium antacid	ETHAMBUTOL serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10049268/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/25861347	unhealthy, 79 years n = 1 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25861347	Disc. AE: Agranulocytosis... AEs leading to discontinuation/dose reduction: Agranulocytosis (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25861347

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/25861347	unhealthy, 79 years n = 1 Health Status: unhealthy Condition: pulmonary tuberculosis Age Group: 79 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25861347

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 OCT1 512 OCT2 647 OCT3 150 OATP1B1 788 OATP2B1 123 OATP1B3 706 MRP3 157 MRP2 383 MRP4 204 BSEP 402 CYP3A 214 UGT1A1 204 UGT1A4 77 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64	P-gp 1537 OCT1 327 OCT2 355 OCTN1 47 OCTN2 50 OAT3 339 OCT3 80 MATE1 135 MATE2 96

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OATP1B3 715	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	moderate [IC50 53.9 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
OATP1B1 803	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	moderate [IC50 57.6 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 8.4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 9.4 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP3A 298	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
UGT1A4 80	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT1A6 141	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT2B15 64	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
OATP2B1 126	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0	no	unlikely Comment: Drug-drug interaction index prediction Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862515/pdf/zac3096.pdf#page=1 Page: 1.0
OCT2 648	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	strong [IC50 253.8 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
OCT1 543	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	strong [IC50 92.6 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 1.4 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 2.9 uM]
OCT3 150	inhibitor 3277 Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0	weak [IC50 4100 uM]	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/57/10/5053.full.pdf#page=1 Page: 1.0
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
UGT1A1 254	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT1A9 121	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT2B7 157	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 88.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
OCTN1 47	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OCTN2 50	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OAT3 339	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_4 Page: 4.0	no
MATE2 96	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
OCT2 355	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	yes
OCT3 80	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17258938/ Page: 1.0	yes
MATE1 135	substrate 3367 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes	likely Comment: DDI index of >0.1 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0
OCT1 327	substrate 3367 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	yes	likely Comment: Drug-drug interaction index prediction Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4877	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4877
ChemicalBook	CB3324345	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3324345
MolPort	MolPort-006-110-202	https://www.molport.com/shop/molecule-link/MolPort-006-110-202
ZINC	ZINC000019364219	http://zinc15.docking.org/substances/ZINC000019364219
eMolecules	31225919	https://www.emolecules.com/cgi-bin/more?vid=31225919

PubMed

Title	Date	PubMed
Mode of action of ethambutol on Mycobacterium tuberculosis, strain H37R V.	1963 Jun	13927289
Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages.	1991 Dec	1667250
In vivo activities of newer rifamycin analogs against Mycobacterium avium infection.	1991 Oct	1662021
Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases.	1992	1406364
Chlorpromazine: a drug potentially useful for treating mycobacterial infections.	1992	1288966
Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?	1992 Dec	1303690
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	1315233
The Garrod Lecture. Understanding the chemotherapy of tuberculosis--current problems.	1992 May	1624388
[Optic nerve neuropathy by ethambutol toxicity].	1999 May	11775861
Bactericidal activities of commonly used antiseptics against multidrug-resistant mycobacterium tuberculosis.	2002	12011515
Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis.	2002 Aug	12121929
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.	2002 Feb	11850167
3-[4'-bromo-(1,1'-biphenyl)-4-yl]-N, N-dimethyl-3-(2-thienyl)-2-propen-1-amine: synthesis, cytotoxicity, and leishmanicidal, trypanocidal and antimycobacterial activities.	2002 Nov	12407118
Ten years of extrapulmonary tuberculosis in a Danish university clinic.	2003	12839152
Evaluation of visual functions in patients on ethambutol therapy for tuberculosis: a prospective study.	2003 Dec	15909750
Familial clustering of rifampin-induced acute renal failure.	2003 Dec	14677899
Activities of moxifloxacin alone and in combination with other antimicrobial agents against multidrug-resistant Mycobacterium tuberculosis infection in BALB/c mice.	2003 Jan	12499213
Ethambutol and optic neuropathy.	2003 Jul	12948256
Ocular ethambutol toxicity.	2003 Nov	14601701
Ethambutol-induced optic neuropathy in a patient with pituitary macroadenoma: case report.	2003 Nov-Dec	15058748
[Unusual therapeutic approach in treatment of pulmonary tuberculosis in six year old girl].	2004	15484863
Pancytopenia due to extensive hemophagocytosis following anti-tubercular treatment.	2004 Feb	14755385
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.	2004 Jan	14645324
The activity of grepafloxacin in two murine models of Mycobacterium avium infection.	2004 Jun	15290460
Ethambutol-induced optic neuritis in patients with end stage renal disease on hemodialysis: two case reports and literature review.	2004 Mar	15287205
Ethambutol-induced acute renal failure.	2004 May	15102986
Synthesis, antimicrobial activity and molecular modeling studies of halogenated 4-[1H-imidazol-1-yl(phenyl)methyl]-1,5-diphenyl-1H-pyrazoles.	2004 Oct 15	15388173
[Septic shock following intracavitary Bacillus Calmette-Guerin therapy for postcystectomy ureteral cancer].	2004 Sep	15518130
[Mycobacterium bovis tuberculosis in a female patient with AIDS].	2005 Apr-Jun	16178466
Multifocal ERG in ethambutol associated visual loss.	2005 Aug	16024847
Rapidly developing optic neuritis secondary to ethambutol: possible mechanism of injury.	2005 Jul	16108516
Multifocal electroretinogram demonstrated macular toxicity associated with ethambutol related optic neuropathy.	2005 Jun	15923521
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	15917538
Phenotypic and molecular characterization of Mycobacterium tuberculosis isolates resistant to both isoniazid and ethambutol.	2005 Jun	15917515
In vitro activity of linezolid, clarithromycin and moxifloxacin against clinical isolates of Mycobacterium kansasii.	2005 Jun	15824090
The role of ultrasound and echo-color Doppler in the diagnosis and follow-up of tuberculosis of the transplanted kidney.	2005 Mar	15906799
Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy.	2005 May	15565293
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.	2005 Nov	16251329
Is liver transplantation advisable for isoniazid fulminant hepatitis in active extrapulmonary tuberculosis?	2005 Nov	16212643
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes.	2005 Sep 19	16171520
Menstrual disorders in nongenital tuberculosis.	2006	17093348
[Meningoencephalitis tuberculosis--primary isolation of resistant M. tuberculosis].	2006	16528937
Fluoroquinolones: an important class of antibiotics against tuberculosis.	2006	16475933
Ethambutol-associated optic neuropathy.	2006 Apr	16710500
[Case of SIADH caused by ethionamide in a patient with pulmonary tuberculosis].	2006 Dec	17240918
Ocular toxicity of ethambutol.	2006 Feb	16495590
Activity of 7-methyljuglone in combination with antituberculous drugs against Mycobacterium tuberculosis.	2006 Nov	16987644
Abnormal multifocal electroretinogram (mfERG) in ethambutol toxicity.	2006 Oct-Dec	17182409
Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy.	2007 Jul	17215265
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	17035089

Patents

Sample Use Guides

In Vivo Use Guide

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

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:02:26 GMT 2023` Edited by `admin` on `Fri Dec 15 15:02:26 GMT 2023`
Record UNII	8G167061QZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ETHAMBUTOL

Official Name

English

Ethambutol [WHO-DD]

Common 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 [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J04AM07