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KMID : 0370220030470020110
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Yakhak Hoeji
2003 Volume.47 No. 2 p.110 ~ p.119
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Pharmacokinetic Modeling and Simulation of the Carrier-Mediated Hepatic Transport of Organic Anions
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이준섭/Lee JS
강민희/김묘경/이명구/정석재/심창구/정연복
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Abstract
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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 Cou nter-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 vivo 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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