Drug Transport VI: Functional Integrity of the Rat Everted Small Intestine with Respect to Passive Transfer

Abstract

Mucosal-to-serosal flux of a number of solutes across the rat everted small intestine was determined as a function of time. Certain compounds including aniline, benzocaine, salicylamide, and antipyrine, which demonstrated initial clearance values of >1 ml./hr., showed little change in permeability over the entire 2-hr. period of study under the experimental conditions. On the other hand, the transfer rates of compounds which were initially cleared at substantially lower rates, such as pralidoxime, riboflavin, methyl orange, eosine blue, and bromthymol blue, increased markedly and continually during the time course of the experiment. Determination of drug transfer rates after the intestine was incubated in buffer revealed that the marked increase in the clearance of these polar compounds with time is due, in part, to a loss of functional integrity of the preparation. The permeability of the everted intestine with respect to riboflavin and methyl orange increased by a factor of about two after only 30 min. of incubation in drug-free buffer solution.