Method for Evaluating Metabolic Functions of Drugs in Bioartificial Liver

  • Park, Yueng-Guen (Laboratory of Tissue Engineering, Korea Cancer Center Hospital, KAERI, Institute for Frontier Medical Science, Kyoto University) ;
  • Hiroo Iwata (Institute for Frontier Medical Science, Kyoto University) ;
  • Seiji Satoh (Department of Gastroenterological Surgery, Kyoto University) ;
  • Takehiko Uesugi (Department of Gastroenterological Surgery, Kyoto University) ;
  • Ryu, Hwa-Won (Faculty of Applied Chemical Engineering Chonnam National University, Institute of Bioindustrial Technology, Chonnam National University)
  • 발행 : 2003.10.01

초록

Lidocaine and galactose loading tests were performed on a bioartificial liver (BAL), an extracorporeal medical device incorporating living hepatocytes in a cartridge without a transport barrier across the membranes. The concentration changes were analyzed using pharmacokinetic equations to evaluate the efficacy and limitation of the proposed method. Lidocaine and galactose were found to be suitable drugs for a quantitative evaluation of the BAL functions, as they did not interact with the plasma proteins or blood vessels, making their concentrations easy to determine. The drug concentration changes after drug loading were easily analyzed using pharmacokinetic equations, and the BAL functions quantitatively expressed by pharmacokinetic parameters, such as the clearance (CL) and galactose elimination capacity (GEC). In addition, these two drugs have already been used in clinical tests to evaluate human liver functions over long periods, and lidocaine CL values and GEC values reported for a normal human liver. Thus, a comparison of the CL and GEC values for the BAL and a natural liver revealed what proportion of normal liver functions could be replaced by the BAL.

키워드

참고문헌

  1. J. Clin. Gastroenterol. v.18 Extracorporeal liver support application to fulminant hepatic failure Sussman,N.L.;G.T.Gislason;J.H.Kelly https://doi.org/10.1097/00004836-199406000-00013
  2. Biotechnol. Bioeng. v.41 Evaluation of a hepatocyte-entrapment hollow fiber bioreactor: A potential bioartificial liver Nyberg,S.L.;R.A.Shatford;M.V.Peshwa;J.G.White;F.B.Cerra;W.S.Hu https://doi.org/10.1002/bit.260410205
  3. Biotechnol. Bioeng. v.73 Effect of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor Tilles,A.W.;H.Baskaran;P.Roy;M.L.Yarmush;M.Toner https://doi.org/10.1002/bit.1071
  4. Biotechnol. Prog. v.16 A novel full-scale flat membrane bioreactor utilizing porcine hepatocytes: cell viability and tissue-specific functions De Bartolo,L.;G.Jarosch Von Schweder;A.Haverich;A.Bader https://doi.org/10.1021/bp990128o
  5. In Vitro Cell Dev. Biol. Anim. v.34 Massive culture of humane liver cancer cells in a newly developed radial flow bioreactor system: utrafine structure of functionally enhanced hepatocarcinoma cell lines Kawada,M.;S.Nagamori;H.Aizaki;K.Fukaya;M.Niiya;T.Matsuura;H.Sujino https://doi.org/10.1007/s11626-998-0092-z
  6. J. Surg. Res. v.82 Evaluation of a hybrid artificial liver using a polyurethane foam packed-bed culture system in dogs Gion,T.;M.Shimada;K.Shirabe;K.Nakazawa;H.Ijima;T.Matsushita;K.Funatsu https://doi.org/10.1006/jsre.1998.5540
  7. ASAIO J. v.45 In Vitro evaluation of metabolic functions of a bioartificial liver Iwata,H.;T.Sajiki;H.Maeda;Y.G.Park;B.Zhu;S.Satoh;T.Uesugi;I,Ikai;Y.Yamaoka;Y.Ikada https://doi.org/10.1097/00002480-199907000-00009
  8. Transplantation v.59 A technique for porcine hepatocytes harvest and description of differentiated metabolic functions in state culture Sielaff,T.D.;W.S.Hu;F.B.Cerra https://doi.org/10.1097/00007890-199505270-00017
  9. J. Pharmacokinet. Biopharm. v.5 Hepatic clearance of drugs: Ⅱ. Experimental evidance for acceptance of the Well-stirred model over the Parallel tube model using lidocaine in the perfused rat liver in situ perparation Pang,K.S.;M.Rowland https://doi.org/10.1007/BF01059689
  10. Ann N. Y. Acad. Sci. v.179 Disposition of lidocaine in normals subjects Rowland,M.;P.D.Thomson;A.Guichard;K.L.Melmon https://doi.org/10.1111/j.1749-6632.1971.tb46915.x
  11. Am. J. Gastroenterol. v.91 The galactose elimination capacity test: A study of the technique based on the analysis of 868 measurements Fabbri,A.;G.Bianchi;E.Motta;M.Brizi;M.Zoli;G.Marchesini
  12. Clinical Pharmacokinetics Concepts and Applications Rowland,M.;T.N.Tozer
  13. J. Pharmacokinet. Biopharm. v.5 Hepatic clearance of drugs: Ⅰ. Theoretical considerations of a Well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocelluar enzymatic activity on hepatic drug clearance Pang,K.S.;M.Rowland https://doi.org/10.1007/BF01059688
  14. Scand, J. Clin. Lab. Invest. v.42 Hepatic galactose elimination kinetics in the intact pig Keiding,S.;S.Johansen;K.Winkler https://doi.org/10.3109/00365518209168082
  15. Am. J. Physiol. v.230 Michaelis-Menten Kinetics of galactose elimination by the isolated perfusaed pig liver Keiding,S.;S.Jihansen,K.Winkler;K.Tonnesen;N.Tygstrup