Details of the Drug

General Information of Drug (ID: DMR87LC)

Drug Name

Ethambutol

Synonyms

Aethambutolum; Diambutol; EMB; Etambutol; Etambutolo; Ethambutolum; Etibi; Miambutol; Myambutol; Purderal; Servambutol; Tibutol; Etambutolo [DCIT]; CL 40881 (dihydrochloride); D-Ethambutol; Etambutol [INN-Spanish]; Ethambutol & EEP; Ethambutol & Propolis; Ethambutol (INN); Ethambutol [INN:BAN]; Ethambutol, meso form; Ethambutol, racemic mixture; Ethambutolum [INN-Latin]; Myambutol (TN); Myambutol (dihydrochloride); Servambutol (TN); Ethambutol, (-)-isomer; D,N,N'-Bis(1-hydroxymethylpropyl)ethylenediamine; D-N,N'-Bis(1-hydroxymethylpropyl)ethylenediamine; D-2,2'-(Ethylenediimino)bis(1-butanol); D-2,2'-(Ethylenediimino)di-1-butanol; (+)-(S,S)-2,2'-(1,2-Ethylenediimino)-di-1-butanol; (+)-2,2'-(Ethylenediimino)di-1-butanol; (+)-N,N'-Bis(1-(hydroxymethyl)propyl)ethylenediamine; (+)-S,S-Ethambutol; (+)-ethambutol; (-)-(R,R)-2,2'-(1,2-Ethylenediimino)-di-1-butanol; (2'S)-2,2'-[Ethane-1,2-diyldi(imino)]dibutan-1-ol; (2R)-2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol; (2R)-2-[2-[[(2R)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol; (2S)-2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol; (2S)-2-[2-[[(2R)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol; (2S,2'S)-2,2'-(ethane-1,2-diyldiimino)dibutan-1-ol; (2S,7S)-2,7-diethyl-3,6-diazaoctane-1,8-diol; (R)-2,2'-(1,2-Ethanediyldiimino)bis-1-butanol; (S,R)-2,2'-(1,2-Ethylenediimino)-di-1-butanol; (S,S)-ethambutol; 2,2'-(1,2-Ethylenediimino)-di-1-butanol; 2,2'-(ethane-1,2-diyldiimino)dibutan-1-ol; 2-[2-(1-hydroxybutan-2-ylamino)ethylamino]butan-1-ol

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary tuberculosis	1B10.Z	Approved	[1]
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Therapeutic Class

Antitubercular Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

204.31

Logarithm of the Partition Coefficient (xlogp)

-0.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 6.3-10.8 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 2-5 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2-4 h [2]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
Bioavailability: The bioavailability of drug is 75-80% [2]
Clearance: The apparent oral clearance of drug is 77.4 L/h [2]
Elimination: Ethambutol is 50% eliminated in the urine as the unmetabolized parent compound, 8 - 15% as inactive metabolites, and 20-22% of a dose is eliminated unchanged in the feces [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.3 hours [5]
Metabolism: The drug is metabolized via the an aldehyde dehydrogenase to an aldehyde metabolite [6]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 122.36009 micromolar/kg/day [7]
Unbound Fraction: The unbound fraction of drug in plasma is 0.18% [8]
Vd: The volume of distribution (Vd) of drug is 76.2 L [2]

Chemical Identifiers

Formula: C10H24N2O2
IUPAC Name: (2S)-2-[2-[[(2S)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol
Canonical SMILES: CC[C@@H](CO)NCCN[C@@H](CC)CO
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
InChIKey: AEUTYOVWOVBAKS-UWVGGRQHSA-N

Cross-matching ID

PubChem CID: 14052
ChEBI ID: CHEBI:4877
CAS Number: 74-55-5
DrugBank ID: DB00330
TTD ID: D08QME
ACDINA ID: D00252

Combinatorial Drugs (CBD)

Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mycobacterium Arabinosyltransferase C (MycB embC)	TT1Q8GP	EMBC_MYCTU	Inhibitor	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Gene/Protein Processing	[10]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Gene/Protein Processing	[11]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Gene/Protein Processing	[11]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Gene/Protein Processing	[11]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Gene/Protein Processing	[12]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Gene/Protein Processing	[12]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Gene/Protein Processing	[12]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Gene/Protein Processing	[12]
Granzyme B (GZMB)	OTPPVIRS	GRAB_HUMAN	Protein Interaction/Cellular Processes	[13]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ethambutol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[14]
Thioguanine	DM7NKEV	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Thioguanine.	Acute myeloid leukaemia [2A60]	[15]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[16]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Ethambutol and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[17]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Cannabidiol.	Epileptic encephalopathy [8A62]	[18]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[19]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[20]
Zalcitabine	DMH7MUV	Moderate	Increased risk of peripheral neuropathy by the combination of Ethambutol and Zalcitabine.	Human immunodeficiency virus disease [1C60-1C62]	[21]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Ethambutol and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[22]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Ethambutol and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[23]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Ethambutol and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[24]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Methotrexate.	Leukaemia [2A60-2B33]	[18]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[25]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Idelalisib.	Mature B-cell leukaemia [2A82]	[26]
Thalidomide	DM70BU5	Moderate	Increased risk of peripheral neuropathy by the combination of Ethambutol and Thalidomide.	Multiple myeloma [2A83]	[21]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Ethambutol and Leflunomide.	Rheumatoid arthritis [FA20]	[23]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[18]
Epirubicin	DMPDW6T	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Epirubicin.	Solid tumour/cancer [2A00-2F9Z]	[14]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Ethambutol and Naltrexone.	Substance abuse [6C40]	[27]
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⏷ Show the Full List of 19 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Docusate sodium	E00563	23673837	Surfactant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Carmellose sodium	E00625	Not Available	Disintegrant
Dextrin	E00359	62698	Binding agent; Diluent; Microencapsulating agent; Stiffening agent; Suspending agent; Viscosity-controlling agent
Hexahydric alcohol	E00083	5780	Diluent; Flavoring agent; Humectant; Plasticizing agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium stearoyl lactylate	E00558	23671849	Emulsifying agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Tergentol	E00569	23682204	Surfactant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone	E00668	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
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⏷ Show the Full List of 20 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ethambutol 100 mg tablet	100 mg	Oral Tablet	Oral
Ethambutol 400 mg tablet	400 mg	Oral Tablet	Oral

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2	Sundell J, Bienvenu E, Birgersson S, Abelo A, Ashton M: Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV. Antimicrob Agents Chemother. 2020 Jan 27;64(2). pii: AAC.01583-19. doi: 10.1128/AAC.01583-19. Print 2020 Jan 27.
3	BDDCS applied to over 900 drugs
4	FDA Approved Drug Products: Myambutol (Ethambutol) Oral Tablet
5	Health Canada Approved Drug Products: Etibi (Ethambutol) Oral Tablets
6	Patterson E, Wall R, Fitzgerald GF, Ross RP, Stanton C: Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metab. 2012;2012:539426. doi: 10.1155/2012/539426. Epub 2012 Apr 5.
7	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
8	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9	The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009 Oct;53(10):4138-46.
10	Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
11	An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
12	Inhibition of cytochrome P450 by ethambutol in human liver microsomes. Toxicol Lett. 2014 Aug 17;229(1):33-40.
13	Detection of Drug-Responsive T-Lymphocytes in a Case of Fatal Antituberculosis Drug-Related Liver Injury. Chem Res Toxicol. 2016 Nov 21;29(11):1793-1795. doi: 10.1021/acs.chemrestox.6b00393. Epub 2016 Nov 9.
14	Cerner Multum, Inc. "Australian Product Information.".
15	Product Information. Aubagio (teriflunomide). Genzyme Corporation, Cambridge, MA.
16	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
17	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
20	Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
21	Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
22	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
23	Canadian Pharmacists Association.
24	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
25	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
26	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
27	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.