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Intestinal Water and Solute Absorption Studies: Comparison of in Situ Perfusion with Chronic Isolated Loops in Rats
Authors:Lu  Hsiao-Hwa  Thomas   James D.  Tukker  Josef J.  Fleisher  David
Affiliation:(1) College of Pharmacy, University of Michigan, Ann Arbor, Michigan, 48109-1065;(2) Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, P.O. Box 80.082 NL-3508TB, Utrecht, The Netherlands
Abstract:The effects of lumenal glucose on jejunal water transport and the influence of glucose-induced water absorption on solute uptake from single-pass perfusions are compared in anesthetized rats in situ and isolated chronic loops in unanesthetized rats in vivo. While the magnitudes of solute membrane permeabilities are consistently higher in the chronic loop system, the effects on water transport and its promotion of jejunal solute uptake are comparable between the two experimental systems. The effect of glucose-induced water absorption on the enhanced/baseline jejunal uptake ratio of the hydrophilic drug, acetaminophen, is greater than that for the lipophilic drug, phenytoin, in both experimental systems. The fact that chronic loop effective solute permeabilities were equivalent to solute membrane permeabilities in situ is consistent with greater lumenal fluid mixing in vivo. In addition, in situ body temperature affects the uptake of phenytoin but not acetaminophen, water, or glucose. This suggests that active and paracellular solute transport is not compromised in situ, while membrane partitioning and diffusion of lipophilic species are more sensitive to experimental conditions.
Keywords:intestinal drug and water absorption  intestinal perfusion  glucose  acetaminophen  phenytoin
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