Inhalation into the lungs provides an important route of administration for some types of drugs. However, measurement of the extent of absorption via the lungs and the nature of the materials absorbed into the pulmonary vasculature is difficult in vivo because of the variable amounts swallowed and subsequently absorbed from the gut lumen. In the perfused-lung model, this problem does not arise.
The surgically isolated respiring lung is perfused with heparinized blood via the pulmonary artery at physiological temperature pressure and blood flow. Effluent blood is either collected at timed intervals (first pass) or allowed to recirculate. Compounds are dosed via the trachea or added directly to the blood. After dosing, aliquots of blood are removed for quantitative analysis up to 3 hours postdose. Volatile compounds/metabolites eliminated via the expired air can be collected throughout the perfusing period with suitable trapping agents. Results are usually expressed as the percent of dose transported from the airways into blood (or vice versa) as parent drug or metabolites. Table 16.1 contains a summary of the major applications of perfused lungs in drug-candidate optimization and drug development.
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