PHARMACOLOGIC DISPOSITION OF INOSINE DIALDEHYDE (NSC-118994) IN MICE, RATS, DOGS, AND MONKEYS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 60  (5) , 555-562
Abstract
The pharmacologic disposition of the antitumor agent inosine dialdehyde (IdA) was studied in mice, rats, dogs and monkeys. 14C-IdA was utilized to follow plasma and tissue levels and patterns of excretion. Plasma radioactivity curves were multiphasic with an initial rapid component (half-life = 12-18 min) followed by a slower decline (half-life = approximately 3 days). As time progressed after injection, an increasing fraction of the total plasma radioactivity was associated with plasma proteins and was trichloroacetic acid (TCA) insoluble. IdA interacts extensively with proteins and small molecules in vivo and in vitro, forming complexes that do not dissociate under physiologic conditions. The pharmacologic disposition of IdA is dependent on the relative extent of IdA interaction with protein macromolecules vs. small transportable molecules. The major route of excretion was urinary with > 50% of the dose excreted during the first 24 h after i.v. administration in all species studied. IdA was recovered in the urine as complexes with urine constituents. There was no preferential uptake of IdA by any organ. All radioactivity remaining 24 h after IdA administration was associated with plasma and cellular proteins and was nondialyzable and TCA insoluble. IdA was not a substrate for aldehyde oxidase and did not inhibit the activity of this enzyme.