Rifampicinを中心とする二次抗結核薬の間欠投与に関する実験的研究
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概要
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Antituberculous effects of Rifampicin (RFP) given intermittently in different methods of administration, dose levels, and at various combinations with secondary antituberculous drugs such as Ethionamide, Ethambutol, Pyrazinamide, Kanamycin, Capreomycin and Viomycin, together with Lividomycin which has lately been under evaluation for its practical usefulness, . were investigated.<BR>All the investigations have been performed on mice inoculated with strain H<SUB>37</SUB>Rv or strain. Schacht which was resistant to INH and SM, and the therapeutic effects of the regimens were assessed by their effects on body weight, survival rate and numbers of viable tubercle bacilli recovered from lungs.<BR>The results o btained were as follows:<BR>In the experiment I and II, the efficac y of RFP given alone, daily and twice weekly, at various doses 20, 10 and 5 mg/kg was tested. The order of efficacy was: 20 mg/kg daily>20mg/kg twice weekly>10 mg/kg daily=10 mg/kg twice weekly=5 mg/kg daily>5 mg/kg twice weekly (Exp. I); and 2 mg/kg daily>2 mg/kg twice weekly= untreated control (Exp. II). To obtain the good results with the intermittent use of RFP, it was suggested to use higher doses of the drug, at least 10 mg/kg.<BR>Even if the drug was given once a week with a dose 20 mg/kg, it was also effective. It was demonstrated clearly that a single weekly dose of 20 mg/kg of RFP was more effective than a daily dose of 5 mg/kg (Exp. III) or 10 mg/kg twice-weekly regimen (Fig.9 & 10), and 20 mg/kg of RFP given in a single dose was almost as effective as that given in two divided doses (Exp. IV).<BR>The once-a-week regimen of RFP 10 mg/kg was inferior to that of 5 mg/kg daily, but was superior to that of 5 mg/kg twice weekly or three times weekly ( Exp. III).<BR>The addition of 40 mg/kg of Pyrazinamide to RFP twice a week gave no clear benefit (Exp. V), but the twice-a-week regimens RFP+Ethionamide 20 mg/kg and RFP+Ethambutol 40 mg/kg produced very good results. In the conditions examined combined effect of Ethionamide was slightly better than Ethambutol (Exp. VI).<BR>There was no significant difference among the effects of Kanamycin 40 mg/kg, Capreomycin 40 mg/kg, Viomycin 40 mg/kg and Lividomycin 40 mg/kg given alone twice weekly, but combined effects uf these drugs to RFP were clearly, observed (Exp. VII).
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