Effect of pulmonary edema on drug transport and binding in rat lung.
The pulmonary absorption and uptake of (35S)phenol red ((35S)PR was measured in anesthetized rats with alpha-naphthylthiourea- (ANTU) induced lung edema. When (35S)PR solution was injected through a tracheal cannula in control animals and the percentage of the tracheal cannula in control animals and the percentage of the dose unabsorbed plotted semilogarithmically against time, an apparent first-order absorption rate was obtained. In contrast, in rats with ANTU-induced edema, the absorption time curve showed at least two different first-order components. Increasing the concentration of (35S)PR from 0.01 to 3 mM resulted in a decrease in the percentage absorption of the compound in controls compared with a relatively constant percentage absorption in edematous lungs. (35S)PR uptake by lung slices from ANTU-treated rats was decreased in the presence of IAA and a N2 atmosphere, and the dye accumulated at a faster rate and to a greater extent than in controls. The results suggest that although energy-dependent drug transport mechanisms remain intact, the porosity of the absorbing membranes and the extent of drug binding in the lung are increased markedly in the presence of edema.
D000818:Animals; D001692:Biological Transport; D004734:Energy Metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives
D004364:Pharmaceutical Preparations; D013890:Thiourea; D010637:Phenolsulfonphthalein