JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Osmolality of Orally Administered Solutions Influences Luminal Water Volume and Drug Absorption in Intestine.

Intestinal water absorption is reportedly influenced by luminal osmolality. In this study, we examined whether differences in the osmolality of the vehicle used for oral administration of drugs influence luminal water volume and drug absorption in the gastrointestinal (GI) tract, by means of in situ rat intestinal closed loop studies using solutions of fluorescein isothiocyanate dextran 4000 (a non-absorbable compound), atenolol (a low-permeability drug), and antipyrine (a high-permeability drug) in various solvents. Determination of the remaining fraction of water revealed the following rank order for water absorption in rat jejunum: purified water > saline > phosphate buffer = isosmotic mannitol solution. The luminal concentration of fluorescein isothiocyanate-dextran 4000 after administration in purified water was significantly increased to 2.5 times the initial dosing concentration. Thus, osmolality-dependent changes in GI water absorption can cause significant changes of drug concentration in the GI fluid, potentially resulting in altered drug absorption characteristics. Indeed, the fraction absorbed of atenolol in jejunum was significantly greater when the drug was administered in purified water than in isosmotic solution. In contrast, no significant change in fraction absorbed of antipyrine was observed. Our results indicate that osmolality-dependent changes in GI water volume may influence drug absorption, especially of low-permeability drugs.

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