抄録
In the previous reports, the authors showed that the serum concentration of free INH and the amount of free INH in urine increased in the case of administration of INH with sulfisoxazol than INH only.
The experiments in vitro and in vivo was tried in order to make those cause clear.
In vitro: When 0.02 M solution of INH and sodium pyruvate reacted at 37°C, pH 7.4 in 0.001 M phosphate buffer, the formation of pyruvic acid isonicotinoyl hydrazon was decreased if SF were mixed in its reaction system.
In vivo: The INH metabolites in urine, which was excreted till 6 hours after administration of INH only or INH with SF to healthy persons, were separated and determined. Free INH and isonicotinic acid were increased and hydrazone type INH (HZ-INH) was decreased considerably but N-isonicotinoyl-N'-acetylhydrazin (INH-Ac) was not decreased when INH
was used with SF. Long acting SF had those effects on INH considerably and the effects of SF on slow inactivator type was greater than rapid inactivator type.
From those experiments, the authors know that the cause of increase of free INH by concomitant administration of SF was not that SF prevented the acetylation of INH which had been thought till now, but that SF prevented the formation of HZ-INH, and that the transformation into hydrazone of INH was not enzymolysis but chemical reaction except the conjugation with glucuronic acid.
