The Distribution of C14 Labeled Isonicotinic Acid Hydrazide in Normal Mice.

Abstract

Isonicotinic acid hydrazide labeled with C14 in the carboxyl position was injd. into CF 1 mice. Total activity representing both unchanged drug and metabolite was measured in various tissues and excreta. The drug was rapidly absorbed following subcut. injn. and distributed to all body tissues. From 75-90% of the injd. material was excreted in the urine during the 1 st 24 hrs., while from 2-8% was excreted through the gastrointestional tract during the same period. Excretion through the bile reached a peak during the 1st 4 hrs. and stopped after 24 hrs. Less than 1% of the injd. activity was recovered as labeled CO2. The liver contained more radioactivity than any other organ and retained significant amts. for as long as 1 week. Chromatograms of brain homogenate indicated that both unchanged drug and isonicotinic acid were present in the brain during the 1st 8 hrs. The lung retained comparatively high concns. of activity after 8 hrs. even when blood levels had fallen to trace amts. Radioactivity approx. equal to 0.015 [mu]g. equivalents of drug/g. of tissue was detectable in the lung for as long as a week after injn. The skin contained sufficient radioactivity throughout the exptl. period to indicate that this organ serves as a major storage depot for the drug. All other organs contained activity during the early hrs. but were negative by 8 hrs. after injn.