Ethambutol - How It Works

CLINICAL PHARMACOLOGY Ethambutol hydrochloride following a single oral dose of 25 mg/kg of body weight, attains a peak of 2 to 5 mcg/mL in serum 2 to 4 hours after administration.

When the drug is administered daily for longer periods of time at this dose, serum levels are similar.

The serum level of ethambutol hydrochloride falls to undetectable levels by 24 hours after the last dose except in some patients with abnormal renal function.

The intercellular concentrations of erythrocytes reach peak values approximately twice those of plasma and maintain this ratio throughout the 24 hours.

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.

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.

From 20 to 22 percent of the initial dose is excreted in the feces as unchanged drug.

No drug accumulation has been observed with consecutive single daily doses of 25 mg/kg in patients with normal kidney function, although marked accumulation has been demonstrated in patients with renal insufficiency.

Ethambutol hydrochloride diffuses into actively growing Mycobacterium cells such as tubercle bacilli.

Ethambutol hydrochloride appears to inhibit the synthesis of one or more metabolites, thus causing impairment of cell metabolism, arrest of multiplication, and cell death.

No cross resistance with other available antimycobacterial agents has been demonstrated.

Ethambutol hydrochloride has been shown to be effective against strains of Mycobacterium tuberculosis but does not seem to be active against fungi, viruses, or other bacteria.

Mycobacterium tuberculosis strains previously unexposed to ethambutol hydrochloride have been uniformly sensitive to concentrations of 8 or less mcg/mL, depending on the nature of the culture media.

When ethambutol hydrochloride has been used alone for treatment of tuberculosis, tubercle bacilli from these patients have developed resistance to ethambutol hydrochloride by in vitro susceptibility tests; the development of resistance has been unpredictable and appears to occur in a step-like manner.

No cross resistance between ethambutol hydrochloride and other antituberculous drugs has been reported.

Ethambutol hydrochloride has reduced the incidence of the emergence of mycobacterial resistance to isoniazid when both drugs have been used concurrently.

An agar diffusion microbiologic assay, based upon inhibition of Mycobacterium smegmatis (ATCC 607) may be used to determine concentrations of ethambutol hydrochloride in serum and urine.

ANIMAL PHPARMACOLOGY Toxicological studies in dogs on high prolonged doses produced evidence of myocardial damage and failure, and depigmentation of the tapetum lucidum of the eyes, the significance of which is not known.

Degenerative changes in the central nervous system, apparently not dose-related, have also been noted in dogs receiving ethambutol hydrochloride over a prolonged period.

In the rhesus monkey, neurological signs appeared after treatment with high doses given daily over a period of several months.