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

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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 (k_g) and first-order intestinal absorption rate constant (k_a) 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 (CL_<a, m>) estimated in the perfusion system were 0.71 and 3.00 μl/min/cm, respectively, for L-glucose and 3-O-MG. The operational luminal volume (V_o), given as CL_<a, m>/k_a, of 39 μl/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 μl/cm, supporting the idea that CL_<a, m> quantitatively reflects the intestinal membrane permeability in vivo and that the luminal volume in vivo is the primary factor which correlates CL_<a, m> and K_a. The V_o of 11 μl/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.
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