COMPARISON OF EXPERIMENTAL METHODS USED IN DRUG ABSORPTION STUDY

Abstract

The purpose of the present study was to understand the characteristics of in situ or in vitro experimental methods used in drug absorption study. Drug permeation parameters obtained from various methods were compared each other and their correlation to in vivo drug absorption was considered. Membrane permeabilities of cephalexin (CEX) calculated from in situ intestinal single-pass perfusion, recirculating perfusion and loop methods were coincided well and, as a whole, they showed the concentration-dependent absorption of CEX. A technique to perfuse the mesenteric blood vessel gave a new parameter for drug absorption, MPT, which represents the mean time required for drug permeation across the intestinal epithelium. Moreover, a rate-limitimg step of drug permeation was determined by the diffusion model analysis. As for the in vitro experiment, the possibility of the drug permeation study using Caco-2 monolayer to simulate in vivo drug absorption was investigated. Permeabilities of passively absorbed drugs to Caco-2 monolayer showed a good correlation with permeabilities calculated from in situ single pass perfusion experiments. However, the permeability of CEX to Caco-2 monolayer was extremely lower than that expected from in situ experiment, suggesting the inappropriate feature of Caco-2 monolayer for predicting the carrier-mediated drug absorption. This may be due to functional differences of Caco-2 monolayer compared to the epithelium of the small intestine.