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In an attempt to explore the quantitative relation in the intestinal absorption between in vivo and a perfusion system, time courses of the remaining fraction in the stomach and that in the small intestine following the intragastric administration of drug solution to rats were simultaneously analyzed by a linear compartment model, using L-glucose and 3-O-methyl-D-glucose (3-O-MG) as model compounds. Derived first-order gastric emptying rate constant (kg) and first-order intestinal absorption rate constant (ka) were 0.025 and 0.018 min-1, respectively, for L-glucose and 0.033 and 0.275 min-1, respectively, for 3-O-MG. Values of the membrane permeability clearance (CLa,m) estimated in the perfusion system were 0.71 and 3.00 microliters/min/cm, respectively, for L-glucose and 3-O-MG. The operational luminal volume (Vo), given as CLa,m/Ka, of 39 microliters/cm for L-glucose was in agreement with the actual luminal volume in vivo estimated by a inulin dilution method and ranging from 20 to 60 microliters/cm, supporting the idea that CLa,m quantitatively reflects the intestinal membrane permeability in vivo and that the luminal volume in vivo is the primary factor which correlates CLa,m and Ka. The Vo of 11 microliters/cm for 3-O-MG was smaller, though still in the same order. It was also shown that the gastrointestinal absorption of 3-O-MG was gastric emptying limited.

journal of pharmacobio-dynamics

Relationship between the first-order intestinal absorption rate constant in vivo and the membrane permeability clearance in a perfusion system: An intragastric administration method in vivo.