Treatment of Experimental Tuberculosis of Guinea Pigs with 4, 4'-Diisoamyloxythiocarbanilide (Isoxyl ®).

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Our laboratory has already confirmed the effectivenees of Isoxyl, a di-substituted derivative of thiourea recently investigated in western countries as a new antituberculous agent, by in vitro and in mouse experiments Particularly, this drug showed a marked prolongation effect of survival time against fatal tuberculous infection of mice. The effect was more than our expectation derived from the in vitro grow th-inhibitory effect of the drug against tubercle bacilli. Basing upon these experiences, a guinea pig experiment was designed by us to examine the therapeutic effect of Isoxyl against advanced tuberculosis of guinea pigs, especially in comparison with streptomycin, kanamycin, and lsoniazid. The combination effect of isoxyl with the above three drugs was also planned. White male guinea pigs weighing about 450 g were used, and they were subcutaneously infected with 0.1 mg of the growth of M. bovium (Ravenel strain) on Ogawe glycerol egg medium. The infection was conducted at the right side of the under abdominal wall. For six weeks after infection, they were nourished with occasional checking of body weight. Then, they were divided into 10 groups as shown in Table 1, and 3 animals of the control group were necropsied to confirm the expected advanced state of tuberculous infection. At the sametime, the drug administration was started against the remaining 9 groups. As for Isoxyl, the daily dose was 100 mg, 50 mg, or 25 mg. In other 3 groups, streptomycin (10 mg). kanamycin (20 mg) or isoniazid (2 mg) was given respectively. In the remaining 3 groups, the above 3 drugs were administered in combination with isoxyl of 25 mg respectively. The drug administration was conducted per os for Isoxyl, and subcutaneously for other drugs, everyday except Sunday for 5 weeks. Three days after the cessation of treatment, all the animals were sacrificed to observe the grade of tuberculous involvement. Observation was made especially concerning the extension of tuberculous lesion in the lungs, liver and spleen, and also concerning spleen weight and swelling of the lymphnodes. The results are shown in Fig.1, Fig.2, Table 2 and Table 3. In every aspect, the remarkable effectiveness of streptomycin, kanamycin and isoniazid was revealed, but no significant effect was demonstrated concerning Isoxyl. The combination effect of Isoxyl with the other 3 drugs was only slight. These results are unexpected in view of our previous experiences on mice. The comparison of experimental conditions between our mouse and guinea pig experiments suggests, however, that Isoxyl might be effective only when the drug administration is initiated soon after infection.
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Treatment of Experimental Tuberculosis of Guinea Pigs with 4, 4'-Diisoamyloxythiocarbanilide (Isoxyl ®).

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