Ethambutol is a synthetic, water-soluble, heat-stable compound, the dextro-isomer of the structure shown below, dispensed as the dihydrochloride salt.
Susceptible strains of Mycobacterium tuberculosis and other myco-bacteria are inhibited in vitro by ethambutol, 1–5 mcg/mL. Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon. Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall. Resistance to ethambutol is due to mutations resulting in overexpression of emb gene products or within the embB structural gene.
Ethambutol is well absorbed from the gut. After ingestion of 25 mg/kg, a blood level peak of 2–5 mcg/mL is reached in 2–4 hours. About 20% of the drug is excreted in feces and 50% in urine in unchanged form. Ethambutol accumulates in renal fail-ure, and the dose should be reduced by half if creatinine clearance is less than 10 mL/min. Ethambutol crosses the blood-brain bar-rier only when the meninges are inflamed. Concentrations in cerebrospinal fluid are highly variable, ranging from 4% to 64% of serum levels in the setting of meningeal inflammation.
As with all antituberculous drugs, resistance to ethambutol emerges rapidly when the drug is used alone. Therefore, ethambutol is always given in combination with other antituberculous drugs.
Ethambutol hydrochloride, 15–25 mg/kg, is usually given as a single daily dose in combination with isoniazid or rifampin. The higher dose is recommended for treatment of tuberculous menin-gitis. The dose of ethambutol is 50 mg/kg when a twice-weekly dosing schedule is used.
Hypersensitivity to ethambutol is rare. The most common serious adverse event is retrobulbar neuritis, resulting in loss of visual acuity and red-green color blindness. This dose-related adverse effect is more likely to occur at dosages of 25 mg/kg/d continued for several months. At 15 mg/kg/d or less, visual disturbances are very rare. Periodic visual acuity testing is desirable if the 25 mg/kg/d dosage is used. Ethambutol is relatively contraindicated in chil-dren too young to permit assessment of visual acuity and red-green color discrimination.