Rifampicinの高desacetylationと副作用について
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Rifampicin today is an indespensable drug along with isoniazid for the control of tuberculosis, and the drug at present is usually prescribed as the combination of rifampicin and isoniazid. In such situation, a few adverse reactions of rifampicin have become apparent. Feverish reaction which is often observed in the first half of the first week of the daily administration, is noticed as an adverse reaction of rifampicin. Previously we have pointed out the following facts: the desacetylation of rifampicin is most active in the first day of daily administration, and then decreases markedly, day by day, within the first week. Therefore, we established the hypothesis that there could be a close relationship between the metabolic production of desacetyl-rifampicin and the fever observed in the first administration.<BR>First of all, the metabolism of rifampicin in man was investigated, as detailed as possible, in 27 hospital patients with lung tuberculosis and 12 healthy persons. The desacetylation of rifampicin in each subject was estimated by determining the ratio of desacetyl-rifampicin to total rifampicin, in the urinary rifampicin.<BR>635 tubercular patients treated with some regimens including rifampicin, and 313 tubercular patients treated without rifampicin as a control were statistically investigated as for the incidence of the feverish reaction.<BR>Since some tubercular patients showed a psychosis of emotional disorder and at the same time a marked increase in the desacetylation, especially, during a prolonged daily administration of rifampicin, the detailed observations on the phenomenon were also carried out through the study.<BR>It is neccessary to clarify first the essential features of the metabolism of rifampicin in man upon the administration of 450 mg rifampicin in a single dose. We will only discuss here our studies on the elimination of the drug and its metabolites in the urine and feaces. The metabolism of rifampicin in a healthy person can be summarized as follows:<BR>1) The greater part of rifampicin, given orally, is transformed into water-soluble metabolites including desacetyl-rifampicin, and then excreted readily in the urine and feaces.<BR>2) Recovery as intact rifampicin is approximately 10% of the dose, and it is found mainly in the urine.<BR>3) Rifampicin glucuronide seems to be the major metabolite, and is found predominantly in the feaces.
- 日本結核病学会の論文
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