Tissue distribution of [ 3H]nicotine in dogs and rhesus monkeys

Abstract

The distribution of [ 3H]-nicotine among different tissues was examined in unanesthetized dogs and monkeys following iv injection of small dose, 100 μg/kg. Nicotine was rapidly distributed throughout tissues. Five minutes after injection, adrenal medulla and cerebral cortex contained high concentrations of nicotine (961 and 505 ng/g for dogs, 1163 and 310 ng/g for monkeys, respectively) and tissue/serum concentration ratios for respective tissue were 13.7 and 7.2 for dogs, 20.7 and 5.5 for monkeys. Concentrations in spleen, adrenal cortex, kidney, and pancreas were relatively high in both species. There were significant regional differences in the concentration in the CNS of both species. Concentrations in various areas of CNS in monkeys were markedly lower than those in dogs. Skeletal muscle concentrations and tissue/serum concentrations ratios in monkeys were almost twice those in dogs. Lower brain content in monkeys may be due to the high affinity of skeletal muscle for nicotine, and may partially explain the lesser sensitivity to nicotine of the monkey as compared to the dog. Thirty minutes after injection, kidney, gastric and intestinal mucosa, and salivary glands had relatively high concentrations in both species and almost all tissue concentrations in monkeys were markedly higher than those in dogs. Lowest levels were found in adipose tissue (10–38 ng/g) in both species. Tissue concentrations of nicotine were roughly proportional to dose. Pentobarbital significantly reduced nicotine concentrations in CNS and adrenal medulla in dogs.