Pharmacokinetic Modeling and Simulation of the Carrier-Mediated Hepatic Transport of Organic Anions

음이온계 약물의 간수송과정에 있어서 담체매개 수송의 약물동력학적 모델링 및 시뮬레이션

  • Published : 2003.04.01

Abstract

The purpose of the present study was to kinetically investigate the carrier-mediated uptake in the hepatic transport of organic anions, and to simulate the ″in vivo counter-transport″ phenomena, using kinetic model which was developed in this study. The condition that the mobility of carrier-ligand complex is greater than that of free carrier is not essential for the occurrence of ″counter-transport″ phenomenon. To examine the inhibitory effects on the initial uptake of a ligand by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. The initial plasma disappearance curves of a organic anion were then kinetically analyzed based on a flow model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). Moreover, ″in vive counter-transport″ phenomena were simulated based on the perfusion model which incorporated the carrier-mediated transport and the saturable intracellular binding. The ″in vivo counter-transport″ phenomena in the hepatic transport of a organic anion were well demonstrated by incorporating the carrier-mediated process. However, the ″in vivo counter-transport″ phenomena may be also explained by the enhancement of back diffusion due to the displacement of intracellular binding. In conclusion, one should be more cautious in interpreting data obtained from so-called ″in vivo counter-transport″ experiments.

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