Drug transport. II. The effect of various cations on the passive transfer of drugs across the everted rat intestine

1. 1. It has been shown in a previous report that replacement of Na⁺ by K⁺ in a Krebs bicarbonate buffer significantly reduced the passive transfer of several water-soluble drugs across the everted rat intestine. As an extension of that study the influence of other cations (vis. NH₄ ⁺, Li⁺, Tris⁺, and guanidine⁺) and the dependence of the drug-transfer rate on K⁺ concentration, have been examined. 2. 2. It is shown that ouabain (1 mM) in the Na⁺ control buffer has no effect on the transfer process of riboflavin, salicylate and sulfanilamide. NH₄ ⁺ and guanidine⁺, as well as K⁺ significantly reduced the transfer of riboflavin while Tris⁺ had no effect; NH₄ ⁺ and K⁺ decreased salicylate transfer and Li⁺ and K⁺ inhibited sulfanilamide transfer. Increasing concentrations of K⁺ caused a progressive decrease in riboflavin transfer. 3. 3. The effect of these various cations on the tissue fluid uptake was examined. Good agreement with previously published results has been obtained. The fluid uptake by rat intestinal segments is strongly influenced by the major cation in the buffer solution and decreases in the following order K⁺ > NH₄ ⁺ > Li⁺ > Na⁺ control > guanidine⁺ > Tris⁺. 4. 4. The inhibition of riboflavin transfer by various cations appears to correlate well with the degree of tissue fluid uptake by intestinal tissue.