YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

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
Download PDF
⟨ Previous Next ⟩

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

References

  1. Pharm. Res. v.13 Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics Yamazaki, M.;Suzuki, H.;Sugiyama, Yl. https://doi.org/10.1023/A:1016077517241
  2. J. Pharm. Sci. v.87 The role of p-glycoprotein and canalicular multispecific organic anion transporter in the hepatobiliary excretion of drugs Kusuhara, H.;Suzuki, H.;Sugiyama, Y. https://doi.org/10.1021/js970100b
  3. J. Pharmacokin. Biopharm. v.18 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. https://doi.org/10.1007/BF01062271
  4. J. Hepatology v.11 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. https://doi.org/10.1016/0168-8278(90)90120-G
  5. Am. J. Physiol. v.207 Initial distribution and rate of uptake of Sulfobromophthalein in the liver Goresky, B. F.
  6. Clin. Sci. Mol. Med. v.51 Kinetics of hepatic uptake unconjugated bilirubin Paumgartner, G.;Reichen, J.
  7. Gastroenterology v.83 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.
  8. Eur. J. Biochem. v.64 Uptake of bromosulfophthalein by isolated liver cells Schwenk, M.;Burr, R.;Schwarz, L.;Pfaff, E. https://doi.org/10.1111/j.1432-1033.1976.tb10287.x
  9. Hepatology v.7 Role of plasma membrane ligand bond organic anions Berk, P. D.;Potter, B. J.;Stremmel, W. https://doi.org/10.1002/hep.1840070131
  10. Biochim. Biophys. Acta v.778 Driving forces in hepato-cellular uptake of phalloidin and cholate Petzinger, E.;Frimmer, M. https://doi.org/10.1016/0005-2736(84)90405-X
  11. Am. J. Physiol. v.256 Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures Petzinger, E.;Muller, N.;Folimann, W.;Deutscher, J.;Kinne, R. K. H.
  12. Gastrointest. Liver Physiol. v.19 Uptake of bumetanide into isolated rat hepatocytes and primary liver cell cultures Petzinger, E.;Muller, N.;Folimann, W.;Deutscher, J.;Kinne, R. K. H.
  13. Biochim. Biophys. Acta v.845 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. https://doi.org/10.1016/0167-4889(85)90058-8
  14. J. Pharmacol. Exp. Ther. v.250 Multispecificity of $Na^+$ -dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles Zimmerli, B.;Valantinas, J.;Meier, P. J.
  15. Proc. Natl. Acad. Sci. USA v.83 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. https://doi.org/10.1073/pnas.83.11.3584
  16. Biochem. Pharmacol. v.30 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.
  17. J. Clin. Invest. v.56 Hepatic organic anion uptake in the rat Scharschmidt, B. F.;Waggondr, J. G.;Berk, P. D. https://doi.org/10.1172/JCI108204
  18. J. Clin. Invest. v.79 Influence of $Cl^-$ 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. https://doi.org/10.1172/JCI112946
  19. Hoppe-Seyler's Z. Physiol. Chem. v.359 Effect of $Na^+$ on bile acid uptake by isolated rat hepatocytes; evidence for a hetero-genous system Anwer, M. S.;Hegner, D.
  20. Hoppe-Seyler's Z. Physiol. Chem. v.359 Effect of organic on bile acid uptake by isolated rat hepatocytes Anwer, M. S.;Hegner, D.
  21. Biochem. Pharmacol. v.30 Transport of dibromosulfophthalein by isolated rat hepatocytes Blom, A.;Keulemans, K.;Meijer, D. K. F. https://doi.org/10.1016/0006-2952(81)90015-0
  22. Biochem. Pharmacol. v.29 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. https://doi.org/10.1016/0006-2952(80)90018-0
  23. J. Hepatol. v.14 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. https://doi.org/10.1016/0168-8278(92)90129-D
  24. J. Clin. Invest. v.56 Hepatic organic anion uptake in the rat Scharschmidt, B. F.;Waggoner, J. G.;Berk, P. D. https://doi.org/10.1172/JCI108204
  25. Arch. Pharm. Res. v.21 Metabolism of an anionic fluorescent dye 1-anilino-8-naphthalene sulfonate (ANS) by rat liver microsomes Chung, Y. B.;Han, K. https://doi.org/10.1007/BF02976756
  26. J. Kor. Pharm. Sci. v.31 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.