Studies with a new antifolate 2,4-diamino-5-adamantyl-6-methylpyrimidine (DAMP): tissue distribution and disposition of 2,4-diamino-5-adamantyl-6-methylpyrimidine and its metabolite

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 205; no. 1; pp. 19 - 26
• Main Authors: Zakrzewski, S F, Dave, C, Mead, L H, Deluomo, D S
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.04.1978
• Subjects: Adamantane - administration & dosage; Adamantane - analogs & derivatives; Adamantane - metabolism; Animals; Bridged-Ring Compounds - metabolism; Folic Acid Antagonists - administration & dosage; Folic Acid Antagonists - metabolism; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intravenous; Liver - metabolism; Liver - ultrastructure; Male; Pyrimidines - administration & dosage; Pyrimidines - metabolism; Rats; Subcellular Fractions - metabolism; Tissue Distribution
• ISSN: 0022-3565; 1521-0103

The pharmacokinetics of a potentially useful antitumor agent, 2,4-diamino-5-adamantyl-6-methylpyrimidine (DAMP) has been studied in rat using 14C-labeled drug. It is reported that DAMP is metabolized rapidly by liver microsomes to an unidentified compound. The metabolite seems to be excreted by liver more rapidly than the unchanged drug, and within 24 hours all radioactivity is eliminated, 80% through kidney and 20% through the bile. Both DAMP, and its metabolite accumulate readily in pancreas and kidney. In contrast, in the brain mostly unchanged DAMP could be detected. The accumulation of the drug in tissues other than liver is much greater after i.v. than after i.p. administration.