Any volatile material, irrespective of its route of administration, has the potential for pulmonary excretion. Certainly, gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. No specialized transport systems are involved in the loss of substances in expired air; simple diffusion across cell membranes is predominant. The rate of loss of gases is not constant; it depends on the rate of respiration and pulmonary blood flow.
The degree of solubility of a gas in blood also will affect the rate of gas loss. Gases such as nitrous oxide, which are not very soluble in blood, will be excreted rapidly, that is, almost at the rate at which the blood delivers the drug to the lungs. Increasing cardiac output has the greatest effect on the removal of poorly soluble gases; for example, doubling the cardiac output nearly doubles the rates of loss. Agents with high blood and tissue solubility, on the other hand, are only slowly transferred from pulmonary capillary blood to the alveoli. Ethanol, which has a relatively high blood gas solubility, is excreted very slowly by the lungs. The arterial concentration of a highly soluble gas falls much more slowly, and its rate of loss depends more on respiratory rate than on cardiac output.
A more detailed discussion of the uptake, distribution, and elimination of compounds administered by inhalation can be found in Chapter 25.
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