Method of screening candidate compounds for susceptibility to biliary excretion in hepatocyte cell cultures

摘要

A method of screening a candidate compound for susceptibility to biliary excretion by a hepatocyte transport protein, the method comprising: (a) providing a cell culture comprising a plurality of hepatocytes and at least one bile canaliculus, at least one of the hepatocytes comprising a transport protein; (b) exposing a candidate compound to the culture; and (c) determining an amount of the candidate compound in the at least one bile canaliculus to thereby screen the candidate compound for susceptibility to biliary excretion by the hepatocyte transport protein, comprising inhibiting expression of the hepatocyte transport protein and detecting an amount of the candidate compound present in the at least one bile canaliculus, wherein the presence of a reduced amount of the candidate compound in the at least one bile canaliculus as compared to an amount of the candidate compound in the at least one bile canaliculus when expression of the hepatocyte transport protein is not inhibited indicates the susceptibility of the candidate compound to biliary excretion by the hepatocyte transport protein.