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Identification
NameEthambutol
Accession NumberDB00330  (APRD00957)
TypeSmall Molecule
GroupsApproved
Description

An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)

Structure
Thumb
Synonyms
(+)-2,2'-(ethylenediimino)di-1-butanol
(+)-ethambutol
(+)-N,N'-bis(1-(hydroxymethyl)propyl)ethylenediamine
(+)-S,S-ethambutol
(2S,7S)-2,7-Diethyl-3,6-diazaoctane-1,8-diol
(S,S)-Ethambutol
EMB
Etambutol
Etambutolo
Ethambutol
Ethambutolum
S,S-Ethambutol
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ethambutol Hydrochloridetablet400 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralREMEDYREPACK INC.2015-06-29Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralSTI Pharma LLC2006-12-15Not applicableUs
Ethambutol Hydrochloridetablet, film coated100 mg/1oralSTI Pharma LLC2006-12-15Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralDepartment Of State Health Services, Pharmacy Branch2006-12-15Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralSTI Pharma2006-12-15Not applicableUs
Ethambutol Hydrochloridetablet, film coated100 mg/1oralDepartment Of State Health Services, Pharmacy Branch2006-12-15Not applicableUs
Ethambutol Hydrochloridetablet, film coated100 mg/1oralSTI Pharma2006-12-15Not applicableUs
Etibi Tab 100mgtablet100 mgoralValeant Canada Lp Valeant Canada S.E.C.1972-12-31Not applicableCanada
Etibi Tab 400mgtablet400 mgoralValeant Canada Lp Valeant Canada S.E.C.1972-12-31Not applicableCanada
Myambutoltablet400 mg/1oralCardinal Health2011-06-27Not applicableUs
Myambutoltablet, film coated400 mg/1oralSTI Pharma, LLC2007-08-10Not applicableUs
Myambutoltablet, film coated100 mg/1oralSTI Pharma, LLC2007-08-10Not applicableUs
Myambutoltablet400 mg/1oralPhysicians Total Care, Inc.2007-08-10Not applicableUs
Myambutoltablet, film coated400 mg/1oralA S Medication Solutions Llc2007-08-10Not applicableUs
Myambutol Tab 100mgtablet100 mgoralLederle Cyanamid Canada Inc.1969-12-311997-01-14Canada
Myambutol Tab 400mgtablet400 mgoralLederle Cyanamid Canada Inc.1969-12-311997-08-14Canada
Myambutol Tablets - 400 mgtablet400 mgoralWyeth Ayerst Canada Inc.1996-11-152002-02-06Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ethambutoltablet, film coated400 mg/1oralPhysicians Total Care, Inc.2010-12-20Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralBarr Laboratories Inc.2001-11-27Not applicableUs
Ethambutol Hydrochloridetablet, film coated100 mg/1oralVersa Pharm Incorporated2015-03-18Not applicableUs
Ethambutol Hydrochloridetablet400 mg/1oralClinical Solutions Wholesale, Llc2009-07-04Not applicableUs
Ethambutol Hydrochloridetablet400 mg/1oralLupin Pharmaceuticals, Inc.2009-07-04Not applicableUs
Ethambutol Hydrochloridetablet100 mg/1oralLupin Pharmaceuticals, Inc.2009-07-04Not applicableUs
Ethambutol Hydrochloridetablet100 mg/1oralREMEDYREPACK INC.2013-03-09Not applicableUs
Ethambutol Hydrochloridetablet100 mg/1oralCarilion Materials Management2009-07-04Not applicableUs
Ethambutol Hydrochloridetablet400 mg/1oralREMEDYREPACK INC.2011-08-01Not applicableUs
Ethambutol Hydrochloridetablet400 mg/1oralAmerican Health Packaging2010-01-14Not applicableUs
Ethambutol Hydrochloridetablet100 mg/1oralREMEDYREPACK INC.2010-11-11Not applicableUs
Ethambutol Hydrochloridetablet, film coated400 mg/1oralVersa Pharm Incorporated2015-03-18Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EtibiValeant Canada Limited
TibutolRefasa
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ethambutol Hydrochloride
1070-11-7
Thumb
  • InChI Key: AUAHHJJRFHRVPV-BZDVOYDHSA-N
  • Monoisotopic Mass: 276.1371335
  • Average Mass: 277.232
DBSALT000446
Categories
UNII8G167061QZ
CAS number74-55-5
WeightAverage: 204.3098
Monoisotopic: 204.183778022
Chemical FormulaC10H24N2O2
InChI KeyInChIKey=AEUTYOVWOVBAKS-UWVGGRQHSA-N
InChI
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
IUPAC Name
(2S)-2-[(2-{[(2S)-1-hydroxybutan-2-yl]amino}ethyl)amino]butan-1-ol
SMILES
CC[C@@H](CO)NCCN[C@@H](CC)CO
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 1,2-aminoalcohols. These are organic compounds containing an alkyl chain with an amine group bound to the C1 atom and an alcohol group bound to the C2 atom.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassAlkanolamines
Direct Parent1,2-aminoalcohols
Alternative Parents
Substituents
  • 1,2-aminoalcohol
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor use, as an adjunct, in the treatment of pulmonary tuberculosis.
PharmacodynamicsEthambutol 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.
Mechanism of actionEthambutol 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.
Related Articles
AbsorptionAbout 75% to 80% of an orally administered dose of ethambutol is absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding20-30%
Metabolism

Hepatic. Up to 15% of administered drug is metabolized to inactive metabolites. The main path of metabolism appears to be an initial oxidation of the alcohol to an aldehydic intermediate, followed by conversion to a dicarboxylic acid.

Route of eliminationDuring the 24-hour period following oral administration of ethambutol hydrochloride approximately 50 percent of the initial dose is excreted unchanged in the urine, while an additional 8 to 15 percent appears in the form of metabolites. From 20 to 22 percent of the initial dose is excreted in the feces as unchanged drug.
Half lifeIn patients with normal renal function, 3 to 4 hours. In patients with impaired renal function, up to 8 hours.
ClearanceNot Available
ToxicityThe most commonly recognized toxic effect of ethambutol is optic neuropathy, which generally is considered uncommon and reversible in medical literature. Other side effects that have been observed are pruritus, joint pain, gastrointestinal upset, abdominal pain, malaise, headache, dizziness, mental confusion, disorientation, and possible hallucinations.
Affected organisms
  • Humans and other mammals
  • Mycobacterium tuberculosis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9157
Blood Brain Barrier-0.7803
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.7142
P-glycoprotein inhibitor INon-inhibitor0.9412
P-glycoprotein inhibitor IINon-inhibitor0.9374
Renal organic cation transporterNon-inhibitor0.8558
CYP450 2C9 substrateNon-substrate0.8575
CYP450 2D6 substrateNon-substrate0.6485
CYP450 3A4 substrateNon-substrate0.8023
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9251
CYP450 3A4 inhibitorNon-inhibitor0.972
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9763
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6982
BiodegradationNot ready biodegradable0.8997
Rat acute toxicity2.2797 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8706
hERG inhibition (predictor II)Non-inhibitor0.8672
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Barr laboratories inc
  • Lupin ltd
  • West ward pharmaceutical corp
  • Sti pharma llc
Packagers
Dosage forms
FormRouteStrength
Tabletoral100 mg/1
Tabletoral400 mg/1
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral400 mg/1
Tabletoral100 mg
Tabletoral400 mg
Prices
Unit descriptionCostUnit
Ethambutol hcl powder5.05USD g
Ethambutol hcl 400 mg tablet1.83USD tablet
Myambutol 400 mg tablet1.83USD tablet
Myambutol 100 mg tablet0.79USD tablet
Ethambutol hcl 100 mg tablet0.59USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point171.5-174.5Wilkinson, R.G. and Shepherd, R.G.; U.S. Patent 3,297,707; January 10,1967; assigned to American Cyanamid Company.
logP-0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.58 mg/mLALOGPS
logP-0.12ALOGPS
logP-0.059ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)14.82ChemAxon
pKa (Strongest Basic)9.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area64.52 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity57.89 m3·mol-1ChemAxon
Polarizability24.47 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis Reference

Sang-Woo Park, “Preparation of ethambutol-diisoniazide methane sulfonic acid salt.” U.S. Patent US4450274, issued February, 1973.

US4450274
General ReferencesNot Available
External Links
ATC CodesJ04AK02J04AM03J04AM06
AHFS Codes
  • 08:16.04
PDB EntriesNot Available
FDA labelDownload (25.3 KB)
MSDSDownload (73.7 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Ethambutol resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
  • Take with food to reduce irritation.

Targets

Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
yes
Actions
inhibitor
General Function:
Involved in transferase activity, transferring pentosyl groups
Specific Function:
Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan
Gene Name:
embC
Uniprot ID:
P72059
Molecular Weight:
117491.0 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Zhang J, Khoo KH, Wu SW, Chatterjee D: Characterization of a distinct arabinofuranosyltransferase in Mycobacterium smegmatis. J Am Chem Soc. 2007 Aug 8;129(31):9650-62. Epub 2007 Jul 14. [PubMed:17630736 ]
  4. Berg S, Starbuck J, Torrelles JB, Vissa VD, Crick DC, Chatterjee D, Brennan PJ: Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J Biol Chem. 2005 Feb 18;280(7):5651-63. Epub 2004 Nov 16. [PubMed:15546869 ]
  5. Sharma K, Gupta M, Pathak M, Gupta N, Koul A, Sarangi S, Baweja R, Singh Y: Transcriptional control of the mycobacterial embCAB operon by PknH through a regulatory protein, EmbR, in vivo. J Bacteriol. 2006 Apr;188(8):2936-44. [PubMed:16585755 ]
  6. Goude R, Amin AG, Chatterjee D, Parish T: The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009 Oct;53(10):4138-46. doi: 10.1128/AAC.00162-09. Epub 2009 Jul 13. [PubMed:19596878 ]
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
yes
Actions
inhibitor
General Function:
Involved in transferase activity, transferring pentosyl groups
Specific Function:
Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan
Gene Name:
embB
Uniprot ID:
P72030
Molecular Weight:
118023.0 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Hazbon MH, Bobadilla del Valle M, Guerrero MI, Varma-Basil M, Filliol I, Cavatore M, Colangeli R, Safi H, Billman-Jacobe H, Lavender C, Fyfe J, Garcia-Garcia L, Davidow A, Brimacombe M, Leon CI, Porras T, Bose M, Chaves F, Eisenach KD, Sifuentes-Osornio J, Ponce de Leon A, Cave MD, Alland D: Role of embB codon 306 mutations in Mycobacterium tuberculosis revisited: a novel association with broad drug resistance and IS6110 clustering rather than ethambutol resistance. Antimicrob Agents Chemother. 2005 Sep;49(9):3794-802. [PubMed:16127055 ]
  4. Lee HY, Myoung HJ, Bang HE, Bai GH, Kim SJ, Kim JD, Cho SN: Mutations in the embB locus among Korean clinical isolates of Mycobacterium tuberculosis resistant to ethambutol. Yonsei Med J. 2002 Feb;43(1):59-64. [PubMed:11854934 ]
  5. Plinke C, Rusch-Gerdes S, Niemann S: Significance of mutations in embB codon 306 for prediction of ethambutol resistance in clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2006 May;50(5):1900-2. [PubMed:16641474 ]
  6. Goude R, Amin AG, Chatterjee D, Parish T: The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009 Oct;53(10):4138-46. doi: 10.1128/AAC.00162-09. Epub 2009 Jul 13. [PubMed:19596878 ]
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
yes
Actions
inhibitor
General Function:
Involved in transferase activity, transferring pentosyl groups
Specific Function:
Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan
Gene Name:
embA
Uniprot ID:
P0A560
Molecular Weight:
115725.0 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Zhang J, Khoo KH, Wu SW, Chatterjee D: Characterization of a distinct arabinofuranosyltransferase in Mycobacterium smegmatis. J Am Chem Soc. 2007 Aug 8;129(31):9650-62. Epub 2007 Jul 14. [PubMed:17630736 ]
  4. Alderwick LJ, Seidel M, Sahm H, Besra GS, Eggeling L: Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem. 2006 Jun 9;281(23):15653-61. Epub 2006 Apr 4. [PubMed:16595677 ]
  5. Berg S, Starbuck J, Torrelles JB, Vissa VD, Crick DC, Chatterjee D, Brennan PJ: Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J Biol Chem. 2005 Feb 18;280(7):5651-63. Epub 2004 Nov 16. [PubMed:15546869 ]
  6. Goude R, Amin AG, Chatterjee D, Parish T: The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009 Oct;53(10):4138-46. doi: 10.1128/AAC.00162-09. Epub 2009 Jul 13. [PubMed:19596878 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09