Quantitative mechanistic studies in simultaneous fluid flow and intestinal absorption using steroids as model solutes

Abstract

The interplay of flow-rate, aqueous boundary layer and membrane permeability coefficients, solute lipophilicity and intestinal length has been quantitatively determined for the in situ situation of bulk fluid flow and concurrent steady-state absorption of steroids in the small intestines of the rat. Seven steroids ranging in 3 orders of magnitude in n-octanol/water partition coefficients were used.The results followed the physical model predictions described by: where Cl/C(0) is the fraction of steroid remaining in the intestinal lumen of length l, r is the effective lumenal radius, Q is the flow-rate, Paq and Pm are the respective aqueous boundary layer and membrane permeability coefficients. The log fraction of steroids remaining in the lumen was linear with intestinal length at various flow rates. The fraction absorbed increased with slower flow-rates at any given length due to the longer residence time. The fraction of steroid absorbed vs log partition coefficient profiles as a function of flow-rate were significantly sigmoidal. The absorption rates of progesterone were aqueous boundary layer-controlled and the less lipophilic hydrocortisone were membrane-controlled. It is significant that the permeability of the aqueous boundary layer is proportional to Q0.44.