음이온계 약물의 간수송과정에 있어서 대향수송의 약물동력학적 모델링 및 시뮬레이션

• 영문명: Pharmacokinetic Modelling and Simulation of the Counter-transport in the Hepatic Transport of Organic Anions
• 발행기관: 대한약학회
• 저자명: 송석길(Sukgil Song) 이준섭(Jun Seup Lee) 정연복(Youn Bok Chung)
• 간행물 정보: 『약학회지』제49권 제4호 (2005년), 275~283쪽, 전체 9쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2005.08.31

영문 초록

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.

키워드

organic anions hepatic transport counter-transport pharmacokinetic modelling simulation