ETHAMBUTOL

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 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

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
Target ID: Probable arabinosyltransferase C Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 7701
Target ID: Probable arabinosyltransferase B Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 7701
Arabinosyltransferase A 4 Target ID: CHEMBL1877 Sources: http://www.drugbank.ca/drugs/DB00330	Inhibitor 7701

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pulmonary tuberculosis 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016320s066lbl.pdf	Primary		Approved 7997	MYAMBUTOL Approved Use pulmonary tuberculosis Launch Date -6.7996799E10

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 1172	inhibitor 1318	inhibitor 1421

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1268 CYP2A6 594 CYP2B6 679 CYP2C8 761 CYP2C19 1215 CYP2E1 761 OCT1 473 OCT2 582 OCT3 139 OATP1B1 698 OATP2B1 107 OATP1B3 613 MRP3 148 MRP2 341 MRP4 194 BSEP 363 CYP3A 175 UGT1A1 174 UGT1A4 67 UGT1A6 94 UGT1A9 102 UGT2B7 130 UGT2B15 56	P-gp 1223 OCT1 294 OCT2 304 OCTN1 37 OCTN2 40 OAT3 299 OCT3 70 MATE1 123 MATE2 91

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OATP1B3 622	inhibitor 2614 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 713	inhibitor 2614 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 1455	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 8.4 uM]
CYP2C19 1277	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	moderate [IC50 9.4 uM]
BSEP 364	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
CYP2B6 845	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP2C8 810	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	no
CYP3A 244	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
MRP2 421	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
MRP4 226	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no
UGT1A4 70	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT1A6 126	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
UGT2B15 56	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	no
OATP2B1 107	inhibitor 2614 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 583	inhibitor 2614 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 488	inhibitor 2614 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 1406	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 1.4 uM]
CYP2E1 841	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	strong [Ki 2.9 uM]
OCT3 139	inhibitor 2614 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 625	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP2C9 1362	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
CYP3A4 1462	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/24910189/ Page: 1.0	weak
UGT1A1 219	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT1A9 107	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
UGT2B7 138	inhibitor 2614 Sources: https://dmd.aspetjournals.org/content/dmd/45/9/1035.full.pdf?with-ds=yes#page=4 Page: 4.0	weak
MRP3 200	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	yes [IC50 88.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
OCTN1 37	substrate 2752 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OCTN2 40	substrate 2752 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	major
OAT3 299	substrate 2752 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_4 Page: 4.0	no
MATE2 91	substrate 2752 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
OCT2 304	substrate 2752 Sources: https://aac.asm.org/content/aac/62/9/e00512-18.full.pdf#page_1 Page: 1.0	yes
OCT3 70	substrate 2752 Sources: https://aac.asm.org/content/aac/60/12/7105.full.pdf#page=1 Page: 1.0	yes
P-gp 1223	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/17258938/ Page: 1.0	yes
MATE1 123	substrate 2752 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 294	substrate 2752 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
[New aspects of tuberculosis therapy].	1975 Feb 22	1124382
Ocular toxicity with ethambutol in tuberculosis patients.	1976 Jul	1026648
[Treatment of severe optic neuritis caused by ethambutol].	1976 Nov	1030352
In vivo activities of newer rifamycin analogs against Mycobacterium avium infection.	1991 Oct	1662021
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
Activities of eighteen antimicrobial regimens against Mycobacterium avium infection in beige mice.	1999 Fall	10566874
Ethambutol-induced psychosis: a case report.	1999 Oct	10533303
A new class of antituberculosis agents.	2000 Aug 24	10966749
Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs.	2000 Feb 1	10609550
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	10649975
Minimal change nephrotic syndrome associated with rifampicin treatment.	2000 Jul	10862648
Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors.	2000 Sep	10980165
Liver function tests in patients of pulmonary tuberculosis using four different drug regimens.	2001 Apr-Jun	11732224
Use of a recombinant strain of Mycobacterium avium expressing beta-galactosidase to evaluate the activities of antimycobacterial agents inside macrophages.	2001 Jan	11120998
Activity of moxifloxacin by itself and in combination with ethambutol, rifabutin, and azithromycin in vitro and in vivo against Mycobacterium avium.	2001 Jan	11120969
Antimycobacterial plant terpenoids.	2001 Nov	11731906
Optic neuropathy after treatment with anti-tuberculous drugs in a subject with Leber's hereditary optic neuropathy mutation.	2001 Sep	11596792
Simple fibroblast-based assay for screening of new antimicrobial drugs against Mycobacterium tuberculosis.	2002 Aug	12121929
Cryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta.	2003 Apr	12722159
Trends in the use of antituberculosis drugs in Spain 1993-1998.	2003 Apr-May	12733476
Antimycobacterial activity of diospyrin derivatives and a structural analogue of diospyrin against Mycobacterium tuberculosis in vitro.	2003 Feb	12562718
Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy.	2003 Jan	12527998
Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to macrolide-containing regimens for treatment of Mycobacterium avium disease.	2003 Jun 15	12792877
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
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.	2004 Jan	14645324
Ethambutol-induced acute renal failure.	2004 May	15102986
[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
Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy.	2005 May	15565293
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes.	2005 Sep 19	16171520
Menstrual disorders in nongenital tuberculosis.	2006	17093348
[Case of SIADH caused by ethionamide in a patient with pulmonary tuberculosis].	2006 Dec	17240918
[Ocular toxicity by the use of ethambutol].	2006 Jul-Aug	17022723
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

Name

Type

Language

ETHAMBUTOL

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