Browse > Article

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

이준섭 (충북대학교병원 약제부)
강민희 (충북대학교 약학대학)
김묘경 (충북대학교 약학대학)
이명구 (충북대학교 약학대학)
정석재 (서울대학교 약학대학)
심창구 (서울대학교 약학대학)
정연복 (충북대학교 약학대학)
Publication Information
YAKHAK HOEJI / v.47, no.2, 2003 , pp. 110-119 More about this Journal
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.
Keywords
Organic anions; hepatic transport; counter-transport; pharmacokinetic modeling; simulation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Metabolism of an anionic fluorescent dye 1-anilino-8-naphthalene sulfonate (ANS) by rat liver microsomes /
[ Chung, Y. B.;Han, K. ] / Arch. Pharm. Res.   DOI
2 Effect of nafenopin on the uptake of bilirubin and sulfobromo-phthalein by isolated perfused rat liver /
[ Gartner, U.;Stockert, R. J.;Levine, W. G.;Wolkoff, A. W. ] / Gastroenterology
3 Kinetic analysis of the dose-dependent hepatic handling of 1-anilino-8-naphthalene sulfonate in rats /
[ Chung, Y. B.;Miyauchi, S.;Sugiyama, Y.;Harashima, H.;Iga, T.;Hanano, M. ] / J. Pharmacokin. Biopharm.   DOI   ScienceOn
4 Uptake of organic anions by isolated rat hepatocytes : a classification in terms of ATP-dependency /
[ Yamazaki, M.;Suzuki, H.;Sugiyama, Y.;Iga, T.;Hanano, M. ] / J. Hepatol.   DOI   ScienceOn
5 Initial distribution and rate of uptake of Sulfobromophthalein in the liver /
[ Goresky, B. F. ] / Am. J. Physiol.
6 Hepatic organic anion uptake in the rat /
[ Scharschmidt, B. F.;Waggoner, J. G.;Berk, P. D. ] / J. Clin. Invest.   DOI
7 Hepatocellular uptake of oleate is energy dependent, sodium linked, and inhibited by an antibody to a hepatocyte plasma membrane fatty acid binding protein /
[ Stremmel, W.;Strohmeyer, S.;Berk, P. D. ] / Proc. Natl. Acad. Sci. USA   DOI   ScienceOn
8 Transport of dibromosulfophthalein by isolated rat hepatocytes /
[ Blom, A.;Keulemans, K.;Meijer, D. K. F. ] / Biochem. Pharmacol.   DOI   ScienceOn
9 Kinetics of hepatic uptake unconjugated bilirubin /
[ Paumgartner, G.;Reichen, J. ] / Clin. Sci. Mol. Med.
10 Multispecificity of <TEX>$Na^+$</TEX> -dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles /
[ Zimmerli, B.;Valantinas, J.;Meier, P. J. ] / J. Pharmacol. Exp. Ther.
11 Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures /
[ Petzinger, E.;Muller, N.;Folimann, W.;Deutscher, J.;Kinne, R. K. H. ] / Gastrointest. Liver Physiol.
12 Effect of organic on bile acid uptake by isolated rat hepatocytes /
[ Anwer, M. S.;Hegner, D. ] / Hoppe-Seyler's Z. Physiol. Chem.
13 Hepatic organic anion uptake in the rat /
[ Scharschmidt, B. F.;Waggondr, J. G.;Berk, P. D. ] / J. Clin. Invest.   DOI
14 Role of plasma membrane ligand bond organic anions /
[ Berk, P. D.;Potter, B. J.;Stremmel, W. ] / Hepatology   DOI
15 Kinetic studies on the deethylation of ethoxybenzamide. A comparative study with isolated hepatocytes and liver microsomes of rat /
[ Lin, J. H.;Sugiyama, Y.;Awazu, S.;Hanano, M. ] / Biochem. Pharmacol.   DOI   ScienceOn
16 Uptake of bromosulfophthalein by isolated liver cells /
[ Schwenk, M.;Burr, R.;Schwarz, L.;Pfaff, E. ] / Eur. J. Biochem.   DOI   ScienceOn
17 Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures /
[ Petzinger, E.;Muller, N.;Folimann, W.;Deutscher, J.;Kinne, R. K. H. ] / Am. J. Physiol.
18 Effect of various organic anions on the plasma disappearance of 1-anilono-8naphthalene sulfonate (ANS) /
[ Chung, Y. B.;Miyauchi, S.;Sugiyama, Y.;Harashima, H.;Iga, T.;Hanano, M. ] / J. Hepatology   DOI   ScienceOn
19 Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics /
[ Yamazaki, M.;Suzuki, H.;Sugiyama, Yl. ] / Pharm. Res.   DOI   ScienceOn
20 Driving forces in hepato-cellular uptake of phalloidin and cholate /
[ Petzinger, E.;Frimmer, M. ] / Biochim. Biophys. Acta   DOI   ScienceOn
21 Kinetic analysis of the hepatic uptake and biliary excretion of 1-anilino-8-naphthalene sulfonate (ANS) in vivo /
[ Bae, W. T.;Chung, Y. B.;Han, K. ] / J. Kor. Pharm. Sci.
22 Effect of <TEX>$Na^+$</TEX> on bile acid uptake by isolated rat hepatocytes; evidence for a hetero-genous system /
[ Anwer, M. S.;Hegner, D. ] / Hoppe-Seyler's Z. Physiol. Chem.
23 Two systems are involved in the sulfobromophthalein uptake by rat liver cells : one is shared with bile salts /
[ Laperche, Y.;Preaux, A. M.;Berthelot, P. ] / Biochem. Pharmacol.
24 Influence of <TEX>$Cl^-$</TEX> on organic anion transport in short-term cultured rat hepatocytes and isolated rat liver /
[ Wolkoff, A. W.;Samuelson, A. C.;Johansen, K. L.;Nakata, R.;Withers, D. M.;Sosiak, A. ] / J. Clin. Invest.   DOI
25 Modified somatostatins as inhibitors of a multispecific transport system for bile acids and phallotoxins in isolated hepatocytes /
[ Ziegler, K.;Frimmer, M.;Kesseler, H.;Damm, J.;Eiermann, V.;Koll, S.;Zarbock, J. ] / Biochim. Biophys. Acta   DOI   ScienceOn
26 The role of p-glycoprotein and canalicular multispecific organic anion transporter in the hepatobiliary excretion of drugs /
[ Kusuhara, H.;Suzuki, H.;Sugiyama, Y. ] / J. Pharm. Sci.   DOI   ScienceOn