RT Journal Article SR Electronic T1 PHYSIOLOGICAL DISPOSITION AND FATE OF C14-LABELLED NICOTINE IN MICE AND RATS JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 91 OP 102 VO 137 IS 1 A1 Eskil Hansson A1 Carl C. Schmiterlöw YR 1962 UL http://jpet.aspetjournals.org/content/137/1/91.abstract AB Mice of 20 g body weight were injected intramuscularly or intravenously with (-)-nicotine-methyl-C14. The distribution was studied with an autoradiographic technique. Within 5 minutes after the injection, high concentration of nicotine was found in brain, adrenal medulla, stomach wall and kidney. Lower concentrations were found in, e.g., blood, liver and skeletal muscles. All tissue concentrations were higher than the blood concentration. The distribution following i.v. and i.m. injections was approximately the same, indicating fast absorption from the intramuscular depot. The same distribution of radioactivity remained in the animals sacrificed at 15 and 30 minutes after the injection. Thereafter the distribution picture changed apparently due to the rapid metabolism of nicotine. The metabolic studies indicated that nicotine is very rapidly metabolized to a compound which presumably is cotinine. A large amount of nicotine is excreted into the stomach via the fundus mucosa and 2 to 3% excreted via the bile of rat during a 6-hour period. Sixty to 80 % of the radioactivity was found in the urine of mice and rats and 8 to 15% in the exhaled carbon dioxide of mice after 24 hours. Chromatographic separation of the urine radioactivity revealed at least 8 nicotine metabolites. Two of these compounds had the same Rf-values on paper chromatograms as cotinine and hydroxycotinine. The significance of the tissue distribution in relation to the pharmacological effects of nicotine and the elucidation of the biological fate of nicotine is discussed.