[New information on the metabolism of isoniazide and rifampicin. Their therapeutical consequences (author's transl)].
The highly bactericidal rifampicin-isoniazide association enabled the shortening of tuberculosis treatment. The authors present the study done on the tolerance to these drugs either alone or in association. Rifampicin on it own is little toxic, apart from a few cases of immuno-allergic accidents connected to intermittent prescriptions. Isoniazide is mainly responsible for hepatic accidents through the medium of metabolite, the acetyl-hydrazin. Acetylation of isoniazide is then completed by a hydrolysis, all the more important that the patient has a rapid acetyling phenotype. The optimal therapeutical period corresponds, 3 hours after a single intake of isoniazide, to a level of 1 to 2 mcg/ml in serum. Hepatic toxicity only appears for a level superior to 2 mcg/ml, mostly for the slow acetylors. Both drugs given together have unchanged cinetics and with adapted dosing of isoniazide the hepatic accidents seem to disappear.
D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D007538:Isoniazid; D012293:Rifampin
Acquisitions récentes sur le métabolisme de l'isoniazide et de la rifampicine. Leurs consequences thérapeutiques.