Short-term distribution of nicotine in the rat lung.

Nicotine is a dibasic amine with a pK(a) of 8.0. At physiological pH roughly 1/4 of the compound is nonionized and able to cross membranes, most notably the alveolar membranes of the lung. Many models of nicotine addiction assume that the time it takes nicotine to pass from inspired air to the blood stream is negligible, resulting in a large peak or bolus in nicotine blood levels following each puff from a cigarette. However, the results of several previous studies have suggested that the lung may act as a short-term depot for nicotine. This was directly investigated in the present study. In anesthetized rats with open-chest and ventilated lungs, 0.4 mg [(3)H] ]nicotine in 50 microl was rapidly injected into the right ventricle of the heart and blood was sampled from the left ventricle. It was found that the [[(3)H]nicotine left the lungs at a significantly slower rate than [(14)C]dextran, a compound which remains in the plasma compartment (3.11% versus 7.71% injected/s for [(3)H]nicotine and [(14)C]dextran, respectively). In similar experiments, lung, heart and brain tissue were obtained at 5s intervals. Significant [(3)H]nicotine remained in the lung throughout the 40 s period, with lung tissue nicotine greater than brain at all time points. These results indicate that the lung may act as a short-term depot for nicotine, delaying and depressing its appearance in the systemic arterial circulation.