A Means of Increasing the Tolerated Dose of Isoniazid in Mice

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Abstract
Attempts were made to increase the tolerated dose of isoniazid (INH) in the DBA strain of mice. INH alone was lethal for 45% of the animals with a 250 mg/kg dose when given orally. With an 8 mg/20 g mouse dose of INH, lethal per se, simultaneous administration of as little as 25 mg glycine and 10 mg sodium glucuronate mono hydrate was sufficient to keep alive all animals tested. By the use of appropriate amount of the 2 detoxyifying chemicals, all mice survived either a single dose of 25 mg INH, or 3 doses of 8 mg daily or 13 doses of 10 mg each given at 72 hour intervals. With larger amounts the mortality was 100%. The blood plasma concentration of INH with a 4 mg dose was 0.13 mg% after 24 hours. The plasma from the mice given the 8 mg INH mixture, after 24 hrs. yielded 0.88 mg%, a 6-fold increase. In the proportions tested, sodium glucuronate and glycine had no effect on the bacteriostatic action of INH in vitro on one human strain of tubercle bacilli.