Abstract
Summary and Conclusions
The toxic effect of isoniazid (INH) in DBA mice has been reduced by solution in several appropriate concentrations of glycerine. A sublethal dose of 4 mg INH (200 mg/kg) in 35% by volume of glucerine (10.9 g glycerol/kg) was administered orally 30 times within 36 days with a higher survival rate and fewer toxic manifestations than the same dose in INH dissolved in water. Doses of 6 or 8 mg INH, lethal per se in aqueous solution, gave 50% mortality after 7 intermittent (twice weekly) administrations when 35% or 50% glycerine solution respectively was employed as solvent. With larger amounts of INH the requisite amount of glycerine lay in the toxic range. The absorption curves indicate that significantly higher blood plasma levels of INH were obtained with the glycerine solutions than with aqueous solutions. In higher concentrations of glycerine there was apparently synergism with INH in the in vitro bacteriostatic action on 2 human strains of Mycobacterium tuberculosis.
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