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Chemistry

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Also known as: 74-55-5, Ethambutolum, Tibutol, Aethambutolum, D-ethambutol, (+)-s,s-ethambutol
Molecular Formula
C10H24N2O2
Molecular Weight
204.31  g/mol
InChI Key
AEUTYOVWOVBAKS-UWVGGRQHSA-N
FDA UNII
8G167061QZ

Ethambutol
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)
Ethambutol is an Antimycobacterial.
1 2D Structure

Ethambutol

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(2S)-2-[2-[[(2S)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol
2.1.2 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
2.1.3 InChI Key
AEUTYOVWOVBAKS-UWVGGRQHSA-N
2.1.4 Canonical SMILES
CCC(CO)NCCNC(CC)CO
2.1.5 Isomeric SMILES
CC[C@@H](CO)NCCN[C@@H](CC)CO
2.2 Other Identifiers
2.2.1 UNII
8G167061QZ
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Dexambutol

2. Emb Fatol

3. Emb Hefa

4. Emb-fatol

5. Emb-hefa

6. Etambutol Llorente

7. Ethambutol Hydrochloride

8. Etibi

9. Hydrochloride, Ethambutol

10. Llorente, Etambutol

11. Miambutol

12. Myambutol

2.3.2 Depositor-Supplied Synonyms

1. 74-55-5

2. Ethambutolum

3. Tibutol

4. Aethambutolum

5. D-ethambutol

6. (+)-s,s-ethambutol

7. (+)-ethambutol

8. (s,s)-ethambutol

9. Myambutol

10. (2s,2's)-2,2'-(ethane-1,2-diylbis(azanediyl))bis(butan-1-ol)

11. Etambutolo [dcit]

12. Ethambutol Hydrochloride

13. Etambutol [inn-spanish]

14. Ethambutolum [inn-latin]

15. S,s-ethambutol

16. Diambutol

17. Chebi:4877

18. (+)-2,2'-(ethylenediimino)di-1-butanol

19. Emb

20. Purderal

21. (+)-n,n'-bis(1-(hydroxymethyl)propyl)ethylenediamine

22. (2s)-2-[2-[[(2s)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol

23. Ethambutol (inn)

24. 8g167061qz

25. (2r)-2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol

26. 1-butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (2s,2's)-

27. 1-butanol,2,2'-(1,2-ethanediyldiimino)bis-, (2s,2's)-

28. Ethambutol [inn]

29. (2s,7s)-2,7-diethyl-3,6-diazaoctane-1,8-diol

30. (2s,2's)-2,2'-(ethane-1,2-diyldiimino)dibutan-1-ol

31. Etambutolo

32. D-2,2'-(ethylenediimino)di-1-butanol

33. D-2,2'-(ethylenediimino)bis(1-butanol)

34. Ethambutol, Racemic Mixture

35. 1-butanol, 2,2'-(ethylenediimino)di-, (+)-

36. D,n,n'-bis(1-hydroxymethylpropyl)ethylenediamine

37. D-n,n'-bis(1-hydroxymethylpropyl)ethylenediamine

38. Ethambutol [inn:ban]

39. (r)-2,2'-(1,2-ethanediyldiimino)bis-1-butanol

40. Ncgc00178864-03

41. 1-butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (s-(r*,r*))-

42. Unii-8g167061qz

43. Hsdb 3078

44. Servambutol (tn)

45. 95e

46. Einecs 200-810-6

47. Spectrum_001058

48. Ethambutol [mi]

49. Spectrum2_001014

50. Spectrum3_000426

51. Spectrum4_000545

52. Spectrum5_000702

53. Ethambutol [hsdb]

54. Ethambutol [vandf]

55. 1-butanol, 2,2'-(1,2-ethanediyldiimino)bis-, (r)-

56. Myambutol (dihydrochloride)

57. Schembl3399

58. Ethambutol [who-dd]

59. Bspbio_002012

60. Kbiogr_001209

61. Kbioss_001538

62. Chembl44884

63. Divk1c_000561

64. Spbio_001167

65. Cl 40881 (dihydrochloride)

66. Dtxsid8023006

67. Kbio1_000561

68. Kbio2_001538

69. Kbio2_004106

70. Kbio2_006674

71. Kbio3_001232

72. Ninds_000561

73. Dtxsid901028179

74. Hy-b0535

75. Bdbm50448407

76. Zinc19364219

77. Db00330

78. Idi1_000561

79. Ncgc00178864-01

80. Ncgc00178864-04

81. Sbi-0051375.p003

82. C06984

83. D07925

84. D94801

85. E-3950

86. Ab00053473_04

87. Ab00053473_05

88. Q412318

89. (s,s)-2,2'-(1,2-ethanediyldiimino)bis-1-butanol

90. Brd-k93231391-300-03-1

91. (+)-(s,s)-2,2'-(1,2-ethylenediimino)-di-1-butanol

92. (2r*,2'r*)-2,2'-(ethane-1,2-diyldiimino)dibutan-1-ol

93. (2s,2s)-2,2-(ethane-1,2-diyldiimino)dibutan-1-ol

94. Ethambutol Dihydrochloride, Antibiotic For Culture Media Use Only

95. (2s)-2-[(2-{[(2s)-1-hydroxybutan-2-yl]amino}ethyl)amino]butan-1-ol

96. (2s)-2-[2-[[(1s)-1-(hydroxymethyl)propyl]amino]ethylamino]butan-1-ol

2.4 Create Date
2005-06-24
3 Chemical and Physical Properties
Molecular Weight 204.31 g/mol
Molecular Formula C10H24N2O2
XLogP3-0.1
Hydrogen Bond Donor Count4
Hydrogen Bond Acceptor Count4
Rotatable Bond Count9
Exact Mass204.183778013 g/mol
Monoisotopic Mass204.183778013 g/mol
Topological Polar Surface Area64.5 Ų
Heavy Atom Count14
Formal Charge0
Complexity109
Isotope Atom Count0
Defined Atom Stereocenter Count2
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameMyambutol
PubMed HealthEthambutol (By mouth)
Drug ClassesAntitubercular
Drug LabelMYAMBUTOL ethambutol hydrochloride is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. The structural formula is:MYAMBUTOL 100 and 400 mg tab...
Active IngredientEthambutol hydrochloride
Dosage FormTablet
RouteOral
Strength400mg; 100mg
Market StatusPrescription
CompanySti Pharma

2 of 2  
Drug NameMyambutol
PubMed HealthEthambutol (By mouth)
Drug ClassesAntitubercular
Drug LabelMYAMBUTOL ethambutol hydrochloride is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. The structural formula is:MYAMBUTOL 100 and 400 mg tab...
Active IngredientEthambutol hydrochloride
Dosage FormTablet
RouteOral
Strength400mg; 100mg
Market StatusPrescription
CompanySti Pharma

4.2 Therapeutic Uses

Antitubercular Agents

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


Ethambutol is indicated in combination with other antituberculosis medications in the treatment of all forms of tuberculosis, including tuberculous meningitis, caused by Mycobacterium tuberculosis. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1334


Ethambutol is used in the treatment of atypical mycobacterial infections, such as Mycobacterium avium complex (MAC). /NOT included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1334


4.3 Drug Warning

Appropriate studies on the relationship of age to the effects of ethambutol have not been performed in children up to 13 years of age. Ethambutol is generally not recommended in children whose visual acuity cannot be monitored (younger than 6 years of age). However, ethambutol should be considered for all children with organisms resistant to other medications, and in whom susceptibility to ethambutol has been demonstrated or is likely.

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1335


The most important adverse effect of ethambutol is optic neuritis with decreases in visual acuity, constriction of visual fields, central and peripheral scotomas, and loss of red-green color discrimination. The extent of ocular toxicity appears to be related to the dose and duration of ethambutol therapy. However, such toxicity also has been reported rarely after only a few days of therapy with the drug, and may represent an idiosyncratic reaction.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


Other adverse effects of ethambutol include dermatitis, pruritus, headache, malaise, dizziness, fever, mental confusion, disorientation, possible hallucinations, joint pain, and rarely anaphylactoid reactions. GI upset, abdominal pain, nausea, vomiting, and anorexia have also occurred occasionally with ethambutol. Peripheral neuritis, with numbness and tingling of the extremities, has been reported infrequently. Increased serum uric acid concentrations and precipitation of acute gout have occurred occasionally in patients receiving ethambutol and are probably the result of decreased renal clearance of urate. Transient impairment of liver function, as indicated by abnormal liver function test results, has also occurred. Cholestatic jaundice, which appeared to be caused by ethambutol, has been reported in at least one patient who received the drug both alone and in conjunction with streptomycin.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


Visual testing should be performed prior to initiating ethambutol therapy and then periodically during therapy with the drug. Testing should be done monthly in patients receiving more than 15 mg/kg daily. Examinations should include ophthalmoscopy, finger perimetry, and testing of color discrimination. Patients developing adverse ocular effects during ethambutol therapy may show subjective visual symptoms either before or simultaneously with decreases in visual acuity. All patients receiving the drug should be questioned periodically about blurred vision and other subjective visual symptoms and should be instructed to report to their physicians any such changes as soon as they are noticed. If substantial changes in visual acuity occur, ethambutol should be discontinued immediately.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


For more Drug Warnings (Complete) data for ETHAMBUTOL (10 total), please visit the HSDB record page.


4.4 Drug Indication

Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. Ethambutol is commonly used in combination with [isoniazid], [rifampin], and [pyrazinamide].


FDA Label


5 Pharmacology and Biochemistry
5.1 Pharmacology

Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. It has a long duration of action as it is administered daily, and a moderate therapeutic window. Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.


5.2 MeSH Pharmacological Classification

Antitubercular Agents

Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. (See all compounds classified as Antitubercular Agents.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
ETHAMBUTOL
5.3.2 FDA UNII
8G167061QZ
5.3.3 Pharmacological Classes
Antimycobacterial [EPC]
5.4 ATC Code

J04AK02

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355


J - Antiinfectives for systemic use

J04 - Antimycobacterials

J04A - Drugs for treatment of tuberculosis

J04AK - Other drugs for treatment of tuberculosis

J04AK02 - Ethambutol


5.5 Absorption, Distribution and Excretion

Absorption

Oral ethambutol is approximately 75-80% orally bioavailable. A 25 mg/kg oral dose of ethambutol reaches a Cmax of 2-5 g/mL, with a Tmax of 2-4 hours. In a separate study, the AUC0-8 varied from 6.3 5.5 h\*mg/L to 10.8 7.6 h\*mg/L depending on CYP1A2 genetic polymorphisms.


Route of Elimination

Ethambutol is 50% eliminated in the urine as the unmetabolized parent compound and 8-15% as inactive metabolites. 20-22% of a dose is eliminated unchanged in the feces.


Volume of Distribution

Patients coinfected with tuberculosis and HIV have an estimated ethambutol volume of distribution of 76.2 L.


Clearance

Patients coinfected with tuberculosis and HIV have an estimated ethambutol oral clearance of 77.4 L/h.


Approximately 75-80% of an oral dose of ethambutol hydrochloride is rapidly absorbed from the GI tract. Absorption is not substantially affected when the drug is administered with food. Following a single oral ethambutol hydrochloride dose of 25 mg/kg, peak serum ethambutol concentrations of 2-5 mcg/mL are attained within 2-4 hours; serum concentrations of the drug are undetectable 24 hours after the dose.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


There is no evidence that accumulation of the drug occurs when ethambutol doses of 25 mg/kg are given once daily in patients with normal renal function. Serum concentrations of the drug are higher and accumulation may occur when ethambutol is used in patients with impaired renal function.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


Ethambutol is widely distributed into most body tissues and fluids. Highest concentrations of the drug are found in erythrocytes, kidneys, lungs, and saliva; lower drug concentrations are found in ascitic fluid, pleural fluid, brain, and CSF. Peak intracellular concentrations of ethambutol in erythrocytes are about twice peak plasma concentrations and maintain this ratio for at least 24 hours after a single oral dose. In patients with meningitis, administration of an oral ethambutol hydrochloride dose of 25 mg/kg has produced peak CSF concentrations of the drug ranging from 0.15-2.0 ug/mL.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


/Ethambutol/ does not penetrate intact meninges, but 10 to 50% may penetrate the meninges of patients with tuberculous meningitis. Volume of distribution is 1.6 liters per kg

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1334


For more Absorption, Distribution and Excretion (Complete) data for ETHAMBUTOL (9 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Ethambutol is mainly oxidized by an aldehyde dehydrogenase to an aldehyde metabolite, followed by conversion to the dicarboxylic acid 2,2'-(ethylinediimino)di-butyric acid.


... Up to 15% is excreted in the form of two metabolites, an aldehyde and a dicarboxylic acid derivative.

Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1161


Ethambutol is partially inactivated in the liver by oxidation to an aldehyde intermediate, 2,2?-(ethylenediimino)-di-butyraldehyde, which is converted to the decarboxylic acid derivative, 2,2?-(ethylenediimino)-di-butyric acid.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


5.7 Biological Half-Life

Ethambutol has a half life of 3.3 hours in patients with normal renal function. In patients with renal failure, the half life could be 7 hours or longer.


The plasma half-life of ethambutol is approximately 3.3 hours in patients with normal renal function. The half-life is prolonged in patients with impaired renal or hepatic function. In patients with renal failure, the half-life may be 7 hours or longer.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


Six normal adult volunteers were administered 15 mg/kg of ethambutol (EMB) by a constant-rate 1-hr infusion. Plasma and urine samples were collected up to 24 and 72 hr, respectively. ... Subsequent postinfusion EMB levels exhibited multiphasic decay. In the 12-hr period following infusion, EMB levels showed biexponential decay. However, 24-hr plasma levels in all subjects were observed to be higher than those predicted using a two-compartment body model. The alpha phase in these subjects had a mean half-life of 8.6 min while the half-life of the beta phase ranged from 2.5 to 3.6 hr (mean 3.1). The half-life of the gamma phase estimated from plasma data points between 12 and 24 hr averaged 1.2 +/- 3.6 hr. A terminal gamma t1/2 of 15.4 +/- 1.7 hr was calculated from 12-72 hr urine data. ... Plasma EMB clearance ranged from 7.47 to 8.87 mL/min/kg (mean 8.57). ...

PMID:7431225 Lee C et al; J Pharmacokinet Biopharm 8 (4): 335-46 (1980)


5.8 Mechanism of Action

Ethambutol diffuses into _Mycobacterium_ cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells.


Ethambutol is bacteriostatic in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit the synthesis of one or more metabolites in susceptible bacteria resulting in impairment of cellular metabolism, arrest of multiplication, and cell death. Ethambutol is active against susceptible bacteria only when they are undergoing cell division.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551


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02-Jan-2021
30-Oct-2024
KGS
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Average Price (USD/KGS)

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Total Quantity (KGS)

Total Value (USD)

Quantity (KGS) & Unit rate (USD/KGS) over time

API Imports and Exports

Importing Country Total Quantity
(KGS)
Average Price
(USD/KGS)
Number of Transactions

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