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In vivo studies of mucosal-serosal transfer in rat jejunum
Authors:D Winne  H Görig  U Müller
Institution:(1) Abteilung für Molekularpharmakologie, Pharmakologisches Institut der Universität, Wilhelmstrasse 56, D-7400 Tübingen 1, Federal Republic of Germany
Abstract:Summary In anesthetized rats, the appearance rates of a series of labeled substances in jejunal venous blood (PHgr B) and serosal bath (PHgr S) were measured in vivo (intestinal blood flow rate 1.5 ml min–1g–1) after intraluminal administration of 0.5 ml buffer solution (initial concentration 1 mmol/l or 1 GBq/l tritiated water) into a closed jejunal segment (length 4–5cm). Between 32% (erythritol) and 93% (salicylic acid) of the administered activity (unchanged substance and possible metabolites) appeared in the intestinal venous blood within 60 min. The fraction recovered from the serosal bath after 15 (60) min was 11 (6) % for tritiated water, 7 (4) % for aniline, 3 (7)% for aminopyrine, 5 (4) % for butanol, 3 (3) % for benzyl alcohol, 2 (4) % for benzylamine, 1–2% for benzoic acid, theophyline, methyl-agr-d-glucopyranoside,l-lysine, antipyrine, and urea, and less than 1% forl-phenylalanine,d-galactose, erythritol, and salicylic acid. During single pass perfusion of a jejunal segment (length 3–4 cm) the fraction of serosal transferPHgr S/(PHgr B+PHgr S) was 19% for tritiated water, 4.9% for antipyrine, 0.5% for benzoic acid, and 0.08% for salicylic acid.Distension of the intestinal wall by administration of 1 ml buffer solution instead of 0.5 ml increased the appearance rate of benzoic acid and antipyrine in intestinal venous blood by a factor of 2 and serosal transfer by a factor of approximately 3. Reduction of blood flow rate from 1.26 to 0.91 ml min–1g–1 decreased the fraction of antipyrine recovered in the intestinal venous blood within 60 min from 84% to 72% and increased the fraction transferred into the serosal bath from 2.3% to 9.1%. A high mucosal-serosal transfer in rat small intestine with intact blood supply can be expected for substances with high epithelial permeability and low binding to plasma proteins.
Keywords:Intestinal absorption  Serosal transfer  Intestinal blood flow  Distention of intestinal wall
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