Influence of Route of Administration on Metabolism of [¹⁴C]Nicotine in Four Species

Abstract

1. The metabolism of [¹⁴C]nicotine has been studied in four species of animals, rabbit, rat, cat and squirrel monkey, after administration by different routes.

2. Intravenous injection of 4 μg/kg [¹⁴C]nicotine every 60 s for 1 h results in peak blood levels of approximately 100 ng/ml in all species but the rabbit. [¹⁴C]Cotinine levels in blood vary widely between species.

3. Subcutaneous injection of 0·4 mg/kg [¹⁴C]nicotine produces similar peak blood nicotine levels but the time course, for a given species, is different.

4. Intragastric instillation of 1 mg/kg [¹⁴C]nicotine to the cat and rabbit results in much lower levels of [¹⁴C]nicotine in blood and relatively high levels of [¹⁴C]-cotinine.

5. Urinary excretion data indicate that, irrespective of route, the squirrel monkey excretes only a small proportion of the dose into urine during the period of experiment, of which the major proportion is [¹⁴C]nicotine. The cat, in contrast, excretes a relatively large proportion of the dose during the experimental period though only a minor proportion of the radioactivity is due to [¹⁴C]nicotine or [¹⁴C]cotinine.

6. All four species are potentially useful for model experiments with nicotine, though metabolism of nicotine by squirrel monkey is most similar to man.