Drugs administered directly into the respiratory tract: modeling of the duration of effective drug levels.

A compartmental model is presented which describes the release of drug from a carrier deposited in the human respiratory tract and the clearance of the drug by mucociliary and nonmucociliary mechanisms. In contrast to the previous experimental and theoretical models, a clear distinction is drawn between the drug still in its "unreleased" form and that present in the form ready for biological activity. The importance of this distinction is shown for considerations regarding the effect of control of rate of release on the duration of residence of drugs and the likely duration of action in the respiratory tract. Both single- and multiple-dose solutions of the model are investigated in numerical simulations. Accumulation of material during chronic administration is shown to lead potentially to excessive amounts of the drug, or its carriers, in lung regions not served by the mucociliary clearance if they are not removed sufficiently rapidly by other clearance mechanisms.