Means of Increasing the Tolerated Dose of Isoniazid in Mice. III. Certain Vitamins

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Abstract
Certain vitamins are effective in increasing the tolerated oral dose of isoniazid (INH) in DBA mice. Pyridoxal-HCl, pyridoxine-HCl, p-aminobenzoic acid, and nicotinic acid, permitted 50% or more, mouse survival in acute toxicity tests with 8 mg INH (400 mg/kg). Only pyridoxal-HCl, in 1-or 2-molar equivalent concentration, protected 100% of mice against this dose. This vitamin in appropriate concentration formed a hydra-zone with INH and the compound containing as much as 20 mg INH/ mouse was tolerated for 8 semi-weekly administrations. Blood plasma levels of INH following administration of the hydrazone were somewhat lower than those after a sublethal dose of INH alone, but were constant and more prolonged, presumably due to gradual in vivo hydrolysis of the hydrazone. Six vitamins, as tested, did not interfere with in vitro bacteriostatic action of INH on one avirulent strain of Mycobacterium, but the pyridoxal isonicotinyl hydrazone per se was as effective as INH alone as a tuberculostatic agent.