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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyEthambutol
Identification
- Name
- Ethambutol
- Accession Number
- DB00330 (APRD00957)
- Type
- Small Molecule
- Groups
- Approved
- 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
Structure for DB00330 (Ethambutol)
- 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
- Product Ingredients
Ingredient UNII CAS InChI Key Ethambutol Hydrochloride QE4VW5FO07 1070-11-7 AUAHHJJRFHRVPV-BZDVOYDHSA-N - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Ethambutol Hydrochloride Tablet 400 mg/1 Oral State of Florida DOH Central Pharmacy 2009-07-01 Not applicable US 
Etibi Tab 100mg Tablet 100 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1972-12-31 Not applicable Canada 
Etibi Tab 400mg Tablet 400 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1972-12-31 Not applicable Canada Myambutol Tablet, film coated 400 mg/1 Oral STI Pharma 2007-08-10 Not applicable US Myambutol Tablet 400 mg/1 Oral Physicians Total Care, Inc. 2007-08-10 Not applicable US Myambutol Tablet, film coated 100 mg/1 Oral STI Pharma 2007-08-10 Not applicable US Myambutol Tablet, film coated 400 mg/1 Oral A S Medication Solutions 2007-08-10 Not applicable US Myambutol Tablet, film coated 400 mg/1 Oral A S Medication Solutions 2007-08-10 2017-06-20 US Myambutol Tablet 400 mg/1 Oral Cardinal Health 2011-06-27 2018-05-31 US Myambutol Tablet, film coated 400 mg/1 Oral A S Medication Solutions 2007-08-10 2017-06-20 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Ethambutol Tablet, film coated 400 mg/1 Oral Physicians Total Care, Inc. 2010-12-20 Not applicable US Ethambutol Hydrochloride Tablet 100 mg/1 Oral Remedy Repack 2010-11-11 2016-10-13 US Ethambutol Hydrochloride Tablet 400 mg/1 Oral Amerincan Health Packaging 2009-11-02 Not applicable US Ethambutol Hydrochloride Tablet, film coated 100 mg/1 Oral Department Of State Health Services, Pharmacy Branch 2006-12-15 Not applicable US Ethambutol Hydrochloride Tablet, film coated 100 mg/1 Oral A S Medication Solutions 2006-12-15 2017-06-20 US Ethambutol Hydrochloride Tablet, film coated 100 mg/1 Oral STI Pharma 2006-12-15 Not applicable US Ethambutol Hydrochloride Tablet, film coated 400 mg/1 Oral Versa Pharm Incorporated 2015-03-18 Not applicable US Ethambutol Hydrochloride Tablet 400 mg/1 Oral Lupin Pharmaceuticals 2009-07-04 Not applicable US Ethambutol Hydrochloride Tablet 100 mg/1 Oral Remedy Repack 2013-03-09 2016-10-13 US Ethambutol Hydrochloride Tablet 400 mg/1 Oral Clinical Solutions Wholsesale 2009-07-04 2017-06-24 US - International/Other Brands
- Etibi (Valeant Canada Limited) / Tibutol (Refasa)
- Categories
- UNII
- 8G167061QZ
- CAS number
- 74-55-5
- Weight
- Average: 204.3098
Monoisotopic: 204.183778022 - Chemical Formula
- C10H24N2O2
- InChI Key
- 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
Pharmacology
- Indication
For use, as an adjunct, in the treatment of pulmonary tuberculosis.
- Associated Conditions
- Pharmacodynamics
Ethambutol 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 action
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.
Target Actions Organism AProbable arabinosyltransferase C inhibitorMycobacterium tuberculosis AProbable arabinosyltransferase B inhibitorMycobacterium tuberculosis AProbable arabinosyltransferase A inhibitorMycobacterium tuberculosis - Absorption
About 75% to 80% of an orally administered dose of ethambutol is absorbed from the gastrointestinal tract.
- Volume of distribution
- Not Available
- Protein binding
20-30%
- 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 elimination
During 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 life
In patients with normal renal function, 3 to 4 hours. In patients with impaired renal function, up to 8 hours.
- Clearance
- Not Available
- Toxicity
The 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
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Aluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Ethambutol resulting in a reduced serum concentration and potentially a decrease in efficacy. Approved, Investigational BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ethambutol. Investigational Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Ethambutol. Approved - Food Interactions
- Take with food to reduce irritation.
References
- Synthesis Reference
Sang-Woo Park, "Preparation of ethambutol-diisoniazide methane sulfonic acid salt." U.S. Patent US4450274, issued February, 1973.
US4450274- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014474
- KEGG Compound
- C06984
- PubChem Compound
- 14052
- PubChem Substance
- 46504788
- ChemSpider
- 13433
- BindingDB
- 50448407
- ChEBI
- 4877
- ChEMBL
- CHEMBL44884
- Therapeutic Targets Database
- DAP000055
- PharmGKB
- PA164784021
- HET
- 95E
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ethambutol
- ATC Codes
- J04AM06 — Rifampicin, pyrazinamide, ethambutol and isoniazid
- J04AM — Combinations of drugs for treatment of tuberculosis
- J04A — DRUGS FOR TREATMENT OF TUBERCULOSIS
- J04 — ANTIMYCOBACTERIALS
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J04AK — Other drugs for treatment of tuberculosis
- J04A — DRUGS FOR TREATMENT OF TUBERCULOSIS
- J04 — ANTIMYCOBACTERIALS
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- AHFS Codes
- 08:16.04 — Antituberculosis Agents
- PDB Entries
- 5nr3
- FDA label
- Download (25.3 KB)
- MSDS
- Download (73.7 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Barr laboratories inc
- Lupin ltd
- West ward pharmaceutical corp
- Sti pharma llc
- Packagers
- Amerisource Health Services Corp.
- A-S Medication Solutions LLC
- Barr Pharmaceuticals
- Belgomex Sprl
- Cardinal Health
- Comprehensive Consultant Services Inc.
- Dept Health Central Pharmacy
- Dispensing Solutions
- Heritage Pharmaceuticals
- Kaiser Foundation Hospital
- Lupin Pharmaceuticals Inc.
- Medisca Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Neuman Distributors Inc.
- Patheon Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Prescript Pharmaceuticals
- Remedy Repack
- Sandhills Packaging Inc.
- Stat Trade Inc.
- Tya Pharmaceuticals
- Versapharm Inc.
- West-Ward Pharmaceuticals
- Dosage forms
Form Route Strength Tablet Oral 100 mg/1 Tablet Oral 400 mg/1 Tablet, film coated Oral 100 mg/1 Tablet Oral 100 mg Tablet Oral 400 mg Tablet, film coated Oral 400 mg/1 - Prices
Unit description Cost Unit Ethambutol hcl powder 5.05USD g Ethambutol hcl 400 mg tablet 1.83USD tablet Myambutol 400 mg tablet 1.83USD tablet Myambutol 100 mg tablet 0.79USD tablet Ethambutol hcl 100 mg tablet 0.59USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 171.5-174.5 Wilkinson, R.G. and Shepherd, R.G.; U.S. Patent 3,297,707; January 10,1967; assigned to American Cyanamid Company. logP -0.3 Not Available - Predicted Properties
Property Value Source Water Solubility 7.58 mg/mL ALOGPS logP -0.12 ALOGPS logP -0.059 ChemAxon logS -1.4 ALOGPS pKa (Strongest Acidic) 14.82 ChemAxon pKa (Strongest Basic) 9.55 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 64.52 Å2 ChemAxon Rotatable Bond Count 9 ChemAxon Refractivity 57.89 m3·mol-1 ChemAxon Polarizability 24.47 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9157 Blood Brain Barrier - 0.7803 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.7142 P-glycoprotein inhibitor I Non-inhibitor 0.9412 P-glycoprotein inhibitor II Non-inhibitor 0.9374 Renal organic cation transporter Non-inhibitor 0.8558 CYP450 2C9 substrate Non-substrate 0.8575 CYP450 2D6 substrate Non-substrate 0.6485 CYP450 3A4 substrate Non-substrate 0.8023 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9251 CYP450 3A4 inhibitor Non-inhibitor 0.972 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9763 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.6982 Biodegradation Not ready biodegradable 0.8997 Rat acute toxicity 2.2797 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8706 hERG inhibition (predictor II) Non-inhibitor 0.8672
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Taxonomy
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Amines
- Direct Parent
- 1,2-aminoalcohols
- Alternative Parents
- Dialkylamines / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 1,2-aminoalcohol / Secondary amine / Secondary aliphatic amine / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Primary alcohol / Organooxygen compound / Alcohol / Aliphatic acyclic compound
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- ethanolamines, ethylenediamine derivative (CHEBI:4877)
Targets
- Kind
- Protein
- Organism
- Mycobacterium tuberculosis
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan.
- Specific Function
- Arabinosyltransferase activity
- Gene Name
- embC
- Uniprot ID
- P9WNL5
- Uniprot Name
- Probable arabinosyltransferase C
- Molecular Weight
- 117488.655 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan.
- Specific Function
- Arabinosyltransferase activity
- Gene Name
- embB
- Uniprot ID
- P9WNL7
- Uniprot Name
- Probable arabinosyltransferase B
- Molecular Weight
- 118020.235 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Arabinosyl transferase responsible for the polymerization of arabinose into the arabinan of arabinogalactan.
- Specific Function
- Arabinosyltransferase activity
- Gene Name
- embA
- Uniprot ID
- P9WNL9
- Uniprot Name
- Probable arabinosyltransferase A
- Molecular Weight
- 115722.825 Da
References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
Drug created on June 13, 2005 07:24 / Updated on June 21, 2018 22:12