Absorption and Excretion of Drugs. XXII. Absorption of Isoniazid and its Derivatives

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1) The stability of sodium (2-isonicotinoylhydrazino) methanesulfonate in isotonic buffer solutions at 37° was found to be stable at low and relatively unstable at neutral pH regions. 2) The stability of isonicotinoyl hydrazones was found to decrease with lowering pH. The facile degradation of these compounds in the stomach should be taken into cosideration for oral administration. 3) Isoniazid was absorbed poorly from the stomach, and rapidly from the intestine. Sodium (2-isonicotinoylhydrazino)methanesulfonate was absorbed more slowly from the stomach and the intestine. 4) Intestinal absorption patterns of isonicotinoylhydrazones were divided into two groups ; slow and rapid ones. Glucose, lactose, glucuronolactone, and sodium pyruvate isonicotinoylhydrazones were hardly absorbed in intact form whereas furyl methyl ketone isonicotinoylhydrazone was absorbed in intact form to a considerable extent. There was a rough relationship between the degree of absorption of these hydrazones and their lipid/water partition characteristics. 5) The fact that intact hydrazones of slow absorptive group are poorly absorbed was further demonstrated by the urinary excretion study using glucose isonicotinoylhydrazone by humans. 6) Suggestion was obtained to use isonicotinoylhydrazones belonging to rapid absorption group effectively by stabilization of the drug in the gut.