Factors influencing absorption and excretion of drugs. IV. Effect of hypertonic and hypotonic solutions on in situ rat intestinal absorption of several drugs.

Abstract

The effect of the hypertonic and hypotonic solutions on the absorption of acetanilide, salicylamide, sulfisoxazole, and quinine from rat small intestine was studied using the in situ perfusion technique. Water net flux into the intestinal lumen occurring in the hypertonic solution diminished the absorption of the drugs. Whereas the enhancement of the absorption of the drugs was observed in the hypotonic solution causing water net flux out of the intestinal lumen. The effect of water net flux on the absorption of the drugs was studied by dividing into the four components. It was found that the solvent drag and rate of blood flow, as the two significant components, played a major role in the absorption of the drugs through the intestinal membrane. The rate of intestinal blood flow played an important role in the absorption of acetanilide and salicylamide, which were lipid soluble and very rapidly absorbed. In the case of the more polar and slowly absorbable quinine, the solvent drag played a significant role. Both blood flow and solvent drag were effective for the absorption of sulfisoxazole, which existed mostly in the ionized form at pH 6.0 and was moderately rapidly absorbed. In addition, it was demonstrated that two other components such as the change of drug concentration in the intestinal lumen and intestinal tissue fluid uptake due to water net flux played a minor role in the in situ intestinal absorption of the drugs.