ABSORPTION OF CARDIAC GLYCOSIDES FROM THE RAT RESPIRATORY TRACT

¹ Department of Pharmacology, University of Missouri—Kansas City, Kansas City, Missouri

The absorption of tritium-labeled cardiac glycosides from the respiratory tract of anesthetized rats was studied after intratracheal administration of 0.1 ml of Krebs-Ringer-phosphate solution (pH 7.4) containing a glycoside. At various times after administration, the lungs and trachea were removed and assayed radiochemically for unabsorbed drug. The half-times for absorption, in minutes, were as follows: digitoxin, 0.3; digoxin, 1.0; ouabain, 67; and dihydroouabain, 87. Absorption rates, expressed as firstorder rate constants, ranked in the same order as the chloroform/water (pH 7.4) partition coefficients of the compounds which were as follows: digitoxin, 123; digoxin, 17; ouabain, 0.004; and dihydroouabain, 0.0008. Thin-layer chromatographic analysis of lung extracts demonstrated that unabsorbed drug was unaltered metabolically. When the initial concentration of the glycosides was varied over a 100-fold range, the absorption rates were directly proportional to concentration. The results suggest that these giycosides are absorbed mainly by passive diffusion across a lipoid-pore membrane and that the pore route is most important for glycosides of lowest lipid solubility.

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