RT Journal Article SR Electronic T1 STUDIES ON THE ABSORPTION, DISTRIBUTION, FATE AND EXCRETION OF 4-C14-LABELED DIPHENYLHYDANTOIN JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 301 OP 314 VO 122 IS 3 A1 Erik L. Noach A1 Dixon M. Woodbury A1 Louis S. Goodman YR 1958 UL http://jpet.aspetjournals.org/content/122/3/301.abstract AB Rats of 300 gm. body weight were injected intravenously with 22 mgm. of 4-C14-labeled Dilantin. Within 5 minutes after the injection, high concentrations of free Dilantin were found in liver, kidney and salivary glands. Lower concentrations were found in brain, body fat and skeletal muscle. All tissue concentrations were higher than the plasma concentration. Dilantin concentrations in all organs decreased to zero within 24 hours; a second peak occurred 1½ hours after drug administration. Comparison of radioactivity measurements with the values for free Dilantin showed that alteration of Dilantin takes place mainly in the liver. After 24 hours, 50 per cent of the administered radioactivity was present in the gastrointestinal tract, and the remainder was found in the urine. Since 93.7 per cent of the radioactivity appeared in the urine within 48 hours, it is concluded that Dilantin and its metabolites are excreted into the gastrointestinal tract and absorbed from there. The presence of Dilantin metabolites in the gastrointestinal tract is due to biliary excretion of these compounds. In cats, Dilantin is secreted by the salivary glands; in rats, such secretion was suggested by the high concentration of Dilantin in these glands. Since the major part of the radioactivity in the bile is present in an acidic extract, whereas neutral urine extracts contain most of the radioactivity, it is assumed tentatively that a conversion of Dilantin metabolites found in the gastrointestinal tract takes place before their urinary excretion.