Rate-Limiting Barriers in Intestinal Absorption

Abstract

Absorption rates of certain poorly lipid-soluble compounds across the isolated rat intestine increase substantially and continually with time (1), apparently due to progressive loss of structural integrity of the epithelium (2). However, loss of structural integrity has little effect on the absorption rates of certain nonpolar, lipid-soluble compounds suggesting that the epithelium is not a critical barrier to the intestinal absorption of such compounds (1). In the present study, this hypothesis was tested directly by comparing the in vitro and in situ flux of various solutes across the normal intestine of the rat and across the rat intestine in which the epithelium was substantially disrupted. The epithelial border was found to be a critical anatomical barrier to the in vitro and in situ intestinal absorption of both charged and uncharged poorly lipid-soluble compounds. However, contrary to the prevailing view (2-4), our studies also showed that the intestinal epithelium is not the rate-limiting barrier to the passive diffusion of rapidly absorbed, freely lipid-soluble compounds.

Methods. Intestinal transfer rates were determined in vitro with everted jeunal segments (10 cm in length) from fasted male Sprague-Dawley rats (weighing about 250 g) using a modification (5) of the method of Crane and Wilson (6), (condition I). Two milliliters of a modified physiologic Krebs bicarbonate buffer (pH 7.4) were placed inside the everted sac (serosal solution) and the entire preparation was placed in 100 ml of buffer solution containing a test compound (mucosal solution) which was continually gassed with O₂:CO₂ (95:5; v/v) and maintained at 37°. The serosal fluid was quantitatively sampled every 10 min for 30 min and each sample was assayed for the test compound. Aniline, salicylamide, salicylate, sulfanilamide, pyridine aldoxime methiodide, riboflavin and methyl orange were assayed as previously described (7).