A New Intestinal Model for Analysis of Drug Absorption and Interactions Considering Physiological Translocation of Contents.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Satoshi AsanoAkihiro Hisaka

Abstract

Precise prediction of drug absorption is key to the success of new drug development and efficacious pharmacotherapy. In this study, we developed a new absorption model, the advanced translocation model (ATOM), by extending our previous model, the translocation model. ATOM reproduces the translocation of a substance in the intestinal lumen using a partial differential equation with variable dispersion and convection terms to describe natural flow and micromixing within the intestine under not only fasted but also fed conditions. In comparison with ATOM, it was suggested that a conventional absorption model, advanced compartmental absorption and transit model, tends to underestimate micromixing in the upper intestine, and it is difficult to adequately describe movements under the fasted and fed conditions. ATOM explains the observed nonlinear absorption of midazolam successfully, with a minimal number of scaling factors. Furthermore, ATOM considers the apical and basolateral membrane permeabilities of enterocytes separately and assumes compartmentation of the lamina propria, including blood vessels, to consider intestinal blood flow appropriately. ATOM estimates changes in the intestinal availability caused by drug interaction as...Continue Reading

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