EXCRETION AND TISSUE DISTRIBUTION STUDIES ON RADIOACTIVE NICOTINE

¹ Department of Pharmacology, University of Tennessee College of Medicine, Memphis 3, Tennessee
² Nuclear Instrument and Chemical Corp., 223 West Erie, Chicago, Illinois
³ Department of Pharmacology, University of Chicago, Chicago 37, Illinois

1. Radioactive nicotine was prepared by growing Nicotiana rustica plants in the presence of radioactive CO₂. After isolation of the radioactive nicotine, studies were performed on its distribution and excretion in the mouse, the urinary excretion in the rat, and on the fixation of nicotine by isolated guinea pig hearts.

2. A spectrophotometric method for the determination of nicotine in urine and in isolated heart perfusates was used to permit a comparison with the values obtained by the radioactive technique.

3. In the mouse the main excretion route of radioactive nicotine is via the urine, and approximately 50 per cent of the radioactivity was recovered from the urine in six hours after injection. The liver showed the highest radioactivity of the organs and tissues studied. No radioactivity was found in the expired air indicating no metabolic breakdown of nicotine to carbon dioxide.

4. In the rat the urinary excretion of radioactive nicotine begins almost immediately after injection and is practically complete after sixteen hours. About 40 per cent of the injected radioactivity is excreted in the urine in three hours, about 85 per cent in six hours and all or almost all is excreted in the urine after sixteen hours. About 25 per cent of the administered drug is found in the unchanged nicotine fraction of the urine collected for the first sixteen hours.

5. When the isolated heart of the guinea pig is perfused with a radioactive nicotine solution an appreciable uptake of the drug occurs only during the initial period of heart block. Almost all of the radioactivity taken up by the heart is released during subsequent perfusion with normal Ringer-Locke solution. Fractionation studies indicate that the isolated heart of the guinea pig does not possess the ability to metabolize nicotine to any appreciable extent.