Arabinosyl transferases, enzymes involved in mycobacterial cell wall biosynthesis. The embB gene product appears to be the main target in Mycobacterium avium and Mycobacterium tuberculosis. In Mycobacterium smegmatis, ethambutol inhibits the synthesis of arabinogalactan and lipoarabinomannan. [1]

The minimum inhibitory concentration (MIC) of ethambutol against Mycobacterium tuberculosis H37Rv is 0.5 μg/ml. [1]
Ethambutol is effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis, M. kansasii, and a number of strains of the M. avium complex. [1]
In M. tuberculosis-infected macrophages, treatment with ethambutol resulted in a reduction of log CFUs. After 3 days of treatment, log CFU values were 4.32 at 3 μg/ml and 4.17 at 6 μg/ml, compared to a control value of 4.8. [1]
The MICs of ethambutol for M. avium (MTCC 1723) and M. smegmatis (MTCC 6) were 15 μg/ml and 0.18 μg/ml, respectively. [1]

Ethambutol hydrochloride can be used in animal modeling to produce a high uric acid model.

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In a mouse efficacy study, ethambutol was administered orally at 100 mg/kg once weekly for 5 weeks, starting 15 days post intravenous infection. This treatment resulted in a log CFU reduction to 4.59, compared to 5.07 in untreated controls. [1]
In another mouse study, ethambutol dosed for 12 weeks with isoniazid, or on alternate days with rifampin and pyrazinamide, resulted in CFUs that were significantly lower than when all four drugs (ETH, PZA, INH, RIF) were dosed together three times weekly. [1]

Mouse Efficacy Study 1:** Mice were infected intravenously. Starting 15 days post-infection, ethambutol was administered orally at a dose of 100 mg/kg, once weekly for 5 weeks. Efficacy was assessed by log CFU reduction. [1]
* **Mouse Efficacy Study 2:** In a separate study, ethambutol was dosed for 12 weeks in combination with other anti-tuberculosis drugs. One group received ETH with isoniazid, while another received ETH on alternate days with rifampin and pyrazinamide. A comparator group received all four drugs (ETH, PZA, INH, RIF) together three times weekly. Efficacy was assessed by CFU counts. [1]

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Mouse Efficacy Study 1: Mice were infected intravenously. Starting 15 days post-infection, ethambutol was administered orally at a dose of 100 mg/kg, once weekly for 5 weeks. Efficacy was assessed by log CFU reduction. [1]
Mouse Efficacy Study 2: In a separate study, ethambutol was dosed for 12 weeks in combination with other anti-tuberculosis drugs. One group received ETH with isoniazid, while another received ETH on alternate days with rifampin and pyrazinamide. A comparator group received all four drugs (ETH, PZA, INH, RIF) together three times weekly. Efficacy was assessed by CFU counts. [1]

Human Pharmacokinetics: In a prospective study of over 100 patients receiving a median daily dose of 24.5 mg/kg ethambutol for 2 months, the following PK parameters were observed: half-life (t½) of 2.6 hours, AUC of 24.9 mg·h/L, Cmax of 5.0 μg/ml, and clearance of 467 ml/min. [1]
FDA Label Information: According to the FDA label, ethambutol reaches a Cmax of 2-5 μg/ml within 2-4 hours after dosing. The drug is undetectable 24 hours after the last dose, except in cases of renal insufficiency. [1]
Mouse Pharmacokinetics: In mice orally dosed with 16 mg/kg ethambutol, the Cmax was 3.5 μg/ml. [1]
Absorption: The oral bioavailability of ethambutol in humans is approximately 75-80%. [1]
Metabolism: Ethambutol is hepatically metabolized to an aldehyde intermediate, which is then converted to a dicarboxylic acid. [1]
Excretion: Ethambutol is primarily renally excreted. Approximately 50% of the drug is excreted unchanged in urine, with 8-15% excreted as metabolites. About 20-22% is excreted in feces. No drug accumulation occurs with single daily doses of 25 mg/kg in patients with normal kidney function, but marked accumulation occurs in patients with renal insufficiency. Ethambutol is also excreted into breast milk. [1]

Animal Toxicity - LD50: The oral LD50 of ethambutol in mice is 2.8 g/kg, and the intraperitoneal LD50 is 2.21 g/kg. The oral LD50 in rats is 4 g/kg. [1]
Animal Toxicity - Neurological: In rhesus monkeys given high doses of ethambutol daily for several months, neurological signs were observed, the severity of which was proportional to drug concentrations in serum. These were correlated with specific serum levels and definite neuroanatomical changes in the CNS. [1]
Animal Toxicity - Cardiac: Toxicological studies in dogs on high, prolonged doses of ethambutol produced evidence of myocardial damage and failure. Focal interstitial carditis was also noted in monkeys receiving high doses for a prolonged period. [1]
Animal Toxicity - Ocular: In dogs, high prolonged doses of ethambutol caused depigmentation of the tapetum lucidum of the eyes, the significance of which is unknown. [1]
Reproductive Toxicology - Teratogenicity: Ethambutol is teratogenic in mice and rabbits when administered in high doses. Birth abnormalities included cleft palate and skeletal malformations. In pregnant mice, a low incidence of cleft palate, exencephaly, and vertebral column abnormalities were observed in fetuses. In rabbits, high doses resulted in fetuses with monophthalmia, limb abnormalities, and hare lip with cleft palate. [1]
Reproductive Toxicology - Fertility: Female rats treated with high doses of ethambutol displayed slight, but not statistically significant, decreases in fertility and litter size. [1]
Human Drug-Drug Interactions: Concurrent administration of ethambutol with aluminum hydroxide-containing antacids may inhibit oral absorption, leading to a 20% reduction in serum concentration and a 13% reduction in urinary excretion. It is recommended to avoid antacids for at least 4 hours following ethambutol administration. A decrease in renal excretion of ethambutol occurs when given together with rifampin. [1]
Human Potential Toxicity - Ocular: Optic neuropathy is the most common toxic effect of ethambutol. Serum concentrations above 10 μg/ml can adversely affect vision. This effect may be dose- and duration-dependent and is generally reversible if the drug is discontinued promptly, though irreversible blindness has been reported. Symptoms may include decreased visual acuity, scotoma, color blindness, and/or visual defects. [1]
Human Potential Toxicity - Hepatic: Hepatotoxicity has been reported with ethambutol use. Baseline and periodic assessment of hepatic function is recommended during treatment. In one study of 19 patients receiving prophylactic ethambutol and pyrazinamide, 7 had elevated liver enzymes leading to treatment discontinuation. [1]
Human Adverse Reactions: Other side effects observed with ethambutol include pruritus, joint pain, gastrointestinal upset, abdominal pain, malaise, headache, dizziness, mental confusion, disorientation, and possible hallucinations. [1]

[1]. Ethambutol. Tuberculosis (Edinb), 2008. 88(2): p. 102-5.

[2]. Rastogi, N., V. Labrousse, and K.S. Goh, In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages. Curr Microbiol, 1996. 33(3): p. 167-75.

[3]. Kaur, D. and G.K. Khuller, In vitro, ex-vivo and in vivo activities of ethambutol and sparfloxacin alone and in combination against mycobacteria. Int J Antimicrob Agents, 2001. 17(1): p. 51-5.

[4]. Kang L, Miao JX, Cao LH, Miao YY, Miao MS, Liu HJ, Xiang LL, Song YG. Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower attenuate adenine- and ethambutol-induced hyperuricaemia in rats. J Ethnopharmacol. 2020 Oct 28;261:113054.

[5]. Pham AQ, Doan A, Andersen M. Pyrazinamide-induced hyperuricemia. P T. 2014 Oct;39(10):695-715.

[6]. Nusanti S, Sari RI, Siregar NC, Sidik M. The Effect of Citicoline on Ethambutol Optic Neuropathy: Histopathology and Immunohistochemistry Analysis of Retina Ganglion Cell Damage Level in Rat Model. J Ocul Pharmacol Ther. 2022 Oct;38(8):584-589.

Ethambutol hydrochloride is a prescription antimicrobial drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of active pulmonary tuberculosis (TB). (Active pulmonary tuberculosis is also known as tuberculosis.) Tuberculosis can be an opportunistic infection (OI) of HIV. Ethambutol hydrochloride is the hydrochloride form of ethambutol, an ethylenediamine derivative with antibacterial activity, particularly effective against mycobacteria. While the exact mechanism of action of ethambutol hydrochloride is not fully understood, it inhibits the transfer of mycolic acid into the bacterial cell wall, thereby hindering bacterial cell growth. The drug may also interfere with RNA synthesis or inhibit other cellular metabolism, thereby preventing cell proliferation and leading to cell death. It is an anti-tuberculosis drug that inhibits the transfer of mycolic acid into the cell wall of Mycobacterium tuberculosis. It may also inhibit spermidine synthesis in mycobacteria. This drug generally has bactericidal activity and can penetrate human cell membranes to exert its lethal effect. (Quoted from Smith and Reynard, Pharmacology Textbook, 1992, p. 863)

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Ethambutol is a generic drug first used in tuberculosis treatment in 1966. It is available as 100 mg and 400 mg tablets. The optimal human dosage is 15 mg/kg daily, or up to 25 mg/kg with monitoring for ocular toxicity. For intermittent therapy, a dose of 30 mg/kg three times per week may be used. [1]
Ethambutol is described as the "fourth drug" for empiric treatment of M. tuberculosis and M. avium. It is used as an adjunct in the treatment of pulmonary tuberculosis, especially in cases of suspected drug resistance. It should not be used alone due to the risk of selecting resistant mutants. The most common treatment regimen involves initial daily therapy with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin three times weekly for 4 months. [1]
Resistance to ethambutol is most commonly associated with mutations in the embB gene, particularly at codon Met306. However, resistant mutants with no changes in emb genes have also been identified. No cross-resistance with other TB agents has been observed. [1]
The standard 15 mg/kg daily dose of ethambutol is considered marginally effective. Some studies suggest it may lack sterilizing activity and could potentially inhibit the sterilizing activities of other TB drugs, at least in the first 14 days of treatment. High relapse rates have been observed when it was used as the primary drug in an intermittent regimen. [1]

276.137

1070-11-7

Ethambutol;74-55-5

14051

White to off-white solid powder

345.3ºC at 760 mmHg

198-200°C

113.7ºC

3.35E-07mmHg at 25°C

2.093

6

4

9

16

109

2

CC[C@@H](CO)NCCN[C@@H](CC)CO.Cl.Cl

AUAHHJJRFHRVPV-BZDVOYDHSA-N

InChI=1S/C10H24N2O2.2ClH/c1-3-9(7-13)11-5-6-12-10(4-2)8-14;;/h9-14H,3-8H2,1-2H3;2*1H/t9-,10-;;/m0../s1

(2S)-2-[2-[[(2S)-1-hydroxybutan-2-yl]amino]ethylamino]butan-1-ol;dihydrochloride

Ethambutol Hydrochloride Ethambutol HCL 4878

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~360.71 mM)
H2O : ≥ 50 mg/mL (~180.36 mM)

Solubility in Formulation 1: 100 mg/mL (360.71 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)