EXPERIMENTAL RE-EVALUATION STUDIES ON ISONICOTINIC ACID HYDRAZIDE lN VITRO AND IN VIVO Ⅰ. In vitro Inhibitory Effects of Isonicotinic Acid Hydrazide (INH) Against Tubercle Bacilli

Of course, it is importanat to discover new antituberculous drugs, but it is also very important to know how present anti-tuberculous drugs should be used for tuberculosis control. It is well known that isonicotinic acid hydrazide(INH) is the most widely used effective drug in chemotherapy of tuberculosis. It seems that a new drug more effective than INH will not be discovered in the near future. From this view point, many investigators are still continuing their efforts to know the best way of using INH, part icularly in optimal dose and mode of administration. In Korea, much of the treatment of pulmonary tuberculosis depends on the use of INH alone, therefore suitable therapeutic methods using INH for control of tuberculosis in this country are urgently required. Under the above mentioned circumstances the authors have made a series of experimental studies on re-evaluation of INH in vitro and in vivo. Two human strains, H₃₇Rv and Kurono, and one bovine strain, Ravenel, were used. Ten day old cultures from Ogawa media were used as inocula throughout the experiments. Proskauer-Beck medium with the addition of 10 percent horse serum was used for determination of inhibitory effects of INH against the above three strains. The following conclusions were reached: 1. Non-contaminated INH solution was obtained by using ten fold dilution or twice dilution methods with sterilized distilled water or Proskauer-Beck medium without autoclaving or Seitz-filtration. 2. Minimum completely inhibitory concentration o INH to human H₃₇Rv strain and Kurono strain was between 0.02mcg per ml. and 0.04 mcg per ml. but to bovine Ravenel strain was around 0.04 mcg per ml. 3. Slide culture method with petroleum ether suspension of the tubercle bacilli is a rapid quantitative method for measuring inhibitory effect of INH against the tubercle bacilli. 4. Under the constant conditions, minimum completely inhibitory concentration of INH against the same strain of tubercle bacilli is always constant. The deep cultures should be observed at least within one week. 5. Microscopic examination of stained slides by slide culture method should be made at three or four days cultivation, because INH activity begins to decrease.