YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetic Modelling and Simulation of the Counter-transport in the Hepatic Transport of Organic Anions

음이온계 약물의 간수송과정에 있어서 대향수송의 약물동력학적 모델링 및 시뮬레이션

  • Song, Suk-Gil (National Research Laboratory (NRL) of PK/PD, College of Pharmacy, Chungbuk National University) ;
  • Lee, Jun-Seup (Chungbuk National University Hospital) ;
  • Chung, Youn-Bok (National Research Laboratory (NRL) of PK/PD, College of Pharmacy, Chungbuk National University)
  • 송석길 (충북대학교 약학대학 국가지정연구실) ;
  • 이준섭 (충북대학교병원 약제부) ;
  • 정연복 (충북대학교 약학대학 국가지정연구실)
  • Published : 2005.08.01
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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 organic anions by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. Effects of bromophenol blue (BPB) or bromosulfophthalein (BSP) on the plasma disappearance curves of a 1-anilino-8-naphthalene sulfonate (ANS) 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 anions 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.

Keywords

References

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