Closed rat jejunal segment in situ: role of pre-epithelial diffusion resistance (unstirred layer) in the absorption process and model analysis.

After intraluminal injection of 0.5 ml buffer solution into closed jejunal segments (length, 3-5 cm) of anesthetized rats the appearance rates of a series of labeled substances in jejunal venous blood were measured for 30 min in situ (initial concentration, 0.02-10 mmol/l or 1 GBq/l tritiated water). The appearance rates quickly rose to a maximum and then declined almost exponentially. Model analysis of the descending of branch of the curves by two one-compartment models (perfect luminal mixing, radial diffusion without convection) revealed a relative pre-epithelial diffusion resistance of nearly 100% for benzoic acid, salicylic acid, L-lysine (0.02 and 1 mmol/l), alpha-methyl-D-glucoside, and L-phenylalanine; 80% to 95% for aniline and butanol; 50% to 80% for benzyl alcohol, theophylline, aminopyrine, antipyrine, dodecanol, and D-galactose; approximately 40% for tritiated water; approximately 30% for L-lysine (10 mmol/l); 10% to 20% for urea and benzylamine; and approximately 4% for erythritol. The shape of the curves was well described by a two-compartment model (intestinal lumen and "tissue", radial luminal diffusion without convection); the variability of the data, however, prevented closer analysis of the parameters of this model. Since pre-epithelial diffusion (unstirred layer) in the closed jejunal segment without peristalsis is the rate limiting step in the absorption process of highly permeant substances, information on intestinal epithelium can be obtained only with poorly permeant substances.