| Indication |
For use in the treatment of pulmonary and extrapulmonary tuberculosis when other antitubercular drugs have failed. |
| Pharmacodynamics |
Ethinamate is bacteriostatic against M. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis
organisms from the lungs of H37Rv infected mice. Drug resistance
developed with continued ethionamide monotherapy, but did not occur when
mice received ethionamide in combination with streptomycin or
isoniazid. |
| Mechanism of action |
Ethionamide may be bacteriostatic or bactericidal in action,
depending on the concentration of the drug attained at the site of
infection and the susceptibility of the infecting organism. Ethionamide,
like prothionamide and pyrazinamide, is a nicotinic acid derivative
related to isoniazid. It is thought that ethionamide undergoes
intracellular modification and acts in a similar fashion to isoniazid.
Isoniazid inhibits the synthesis of mycoloic acids, an essential
component of the bacterial cell wall. Specifically isoniazid inhibits
InhA, the enoyl reductase from Mycobacterium tuberculosis, by
forming a covalent adduct with the NAD cofactor. It is the INH-NAD
adduct that acts as a slow, tight-binding competitive inhibitor of InhA. |
| Absorption |
Essentially completely absorbed following oral administration and
not subjected to any appreciable first pass metabolism. Bioavailability
approximately 100%. |
| Volume of distribution |
- 93.5 L [healthy volunteers]
|
| Protein binding |
Approximately 30% bound to proteins. |
| Metabolism |
Hepatic and extensive. Metabolized to the active metabolite
sulfoxide, and several inactive metabolites. The sulphoxide metabolite
has been demonstrated to have antimicrobial activity against Mycobacterium tuberculosis. |
| Route of elimination |
Less than 1% of the oral dose is excreted as ethionamide in urine.
Ethionamide is extensively metabolized to active and inactive
metabolites. |
| Half life |
2 to 3 hours |
| Clearance |
Not Available |
| Toxicity |
Symptoms of overdose include convulsions, nausea, and vomiting. |
