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

Abstract

1 The distribution and metabolism of (2′-¹⁴C) nicotine given as a series of small intravenous injections (4 μg/kg every 60 s for 20 min) have been studied in the cat. 2 Blood concentrations of (¹⁴C) 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 μg/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 (¹⁴C) nicotine and 0.05% as (¹⁴C) cotinine was excreted. 5 Gastric juice after 2 h contained significant amounts of activity which was almost entirely composed of (¹⁴C) nicotine and (¹⁴C) cotinine. 6 There were significant regional differences in the concentration of (¹⁴C) 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 (¹⁴C) nicotine than the whole mid brain. (¹⁴C) Cotinine concentrations were highest in the cerebellum.