EXPERIMENTAL RE-EVALUATION STUDIES ON ISONICOTINIC ACID HYDRAZIDE lN VITRO AND IN VIVO Ⅲ. Experimental Studies on Comparison of Therapeutic Effects with Various Doses of Isonicotinic Acid Hydrazide (INH) in Mice Infected with the H37 Rv Strain.

Abstract

It is well known that proper treatment with INH alone is effective, as sell as combined therapy Recently high doses of INH have been recommended by many investigators. For the purpose of studying therapeutic effects of anti-tuberculous drugs the mouse is an useful experimental animal. If the experiments are performed properly, the results from experimental tuberculosis in mice offers valuable information applicable to man. Many investigators determine the efficacy of anti-tuberculous drugs by examining multiplication of viable tubercle bacilli recovered from the spleen of mice. But, as it requires quite a long period of observation to evaluate the effectiveness of anti-tuberculous drugs in the experimental animals, in our opinion the lung is the only suitable organ for the above mentioned purpose. The following results were reached in our experiments in the SM-strain mice infected with H<sub>37</sub>Rv strain for comparisons of the therapeutic effects with various oral doses of INH and development of INH resistant tubercle bacilli: 1. The therapeutic effects of INH to tuberculous mice depend on the amounts of INH, large dosage offers better therapeutic efficacy. But, the differences in anti-tuberculous effects of INH were only slight between larger than optimal dose and optimal dose. 2. Even though the tubercle bacilli in vivo do not multiply by INH treatment, the dosage is the more the development of INH resistant was the more frequent. 3. If we expect the best therapeutic effect of INH and protect the development of INH resistant tubercle bacilli, higher than optimal doses of INH should be criticized. 4. Toxicity of INH is not the only problem to be considered in determining the high therapeutic amount of INH. 5. The present usual dosage of INH should be re-evaluated and also the term and concept of high dosage of INH in chemotherapy of tuberculosis should be reviewed. We propose the routine doses of INH should be increased from the present doses for the effective treatment of tuberculosis.