Estimation of P-glycoprotein-mediated efflux in the oral absorption of P-gp substrate drugs from simultaneous analysis of drug dissolution and permeation.
Authors: Kataoka M, Yokoyama T, Masaoka Y, Sakuma S, Yamashita S
Abstract
The purpose of this study was to establish an in vitro system that evaluates the effects of P-glycoprotein (P-gp)-mediated efflux on the oral absorption of P-gp substrates. An in vitro system (dissolution/permeation system, D/P system) was developed that consisted of apical and basal chambers and a Caco-2 cell monolayer mounted between the chambers. Both sides of the monolayer were filled with physiological solution and were stirred at 200rpm. The dissolution in the apical medium and permeation to the basal medium were monitored for 2h after P-gp substrates were applied to the apical side of the system. When erythromycin existed in the apical medium, the permeations of fexofenadine and talinolol were signific...
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