Metabolism of small multiple doses of (14C) nicotine in the cat.

1. The distribution and metabolism of (2'-(14)C) nicotine given as a series of small intravenous injections (4 mug/kg every 60 s for 20 min) have been studied in the cat.2. Blood concentrations of ((14)C) nicotine reached a maximum of 100 ng/ml at 20 min whereas blood concentrations of cotinine were maximal shortly afterwards.3. The maximum concentration of nicotine in the blood was greater than that obtained by giving the same total dose as a continuous infusion ((4 mug/kg)/min for 20 min).4. Urinary excretion accounted for 90% of the total multiple dose in 72 hours. After 24 h, however, only 2.5% of the radioactivity as ((14)C) nicotine and 0.05% as ((14)C) cotinine was excreted.5. Gastric juice after 2 h contained significant amounts of activity which was almost entirely composed of ((14)C) nicotine and ((14)C) cotinine.6. There were significant regional differences in the concentration of ((14)C) nicotine in the brain; amounts were greatest in cerebral hemispheres and smallest in the spinal cord. The hypothalamus and thalamus contained significantly higher concentrations of ((14)C) nicotine than the whole mid brain. ((14)C) Cotinine concentrations were highest in the cerebellum.