Influence of D-glucose-induced water absorption on rat jejunal uptake of two passively absorbed drugs.

The intestinal absorption of D-glucose is coupled to transepithelial sodium transport and this process generates intestinal water absorption. In situ jejunal perfusions were performed in rats to determine the extent of water transport as a function of perfusion flow rate, perfusate osmolality, and D-glucose concentration. Jejunal perfusions of iso-osmolar D-glucose, at flow rates and concentrations representative of the fed state, increased the dimensionless membrane permeabilities of the analgesic acetaminophen from 0.6 to 1.4, and that of the corticosteroid prednisolone from 1.6 to 2.2. This increase is less important for the more hydrophobic prednisolone since its baseline permeability (1.6) is indicative of complete uptake from solution, while the lower baseline permeability (0.6) of the more hydrophilic acetaminophen represents incomplete membrane uptake. The results suggest that nutrient-induced water transport can enhance jejunal uptake of small hydrophilic solutes. This phenomenon may contribute to variability in the absorption of drugs in this physicochemical class during the fed state.