Patent ID: 6780580
Filing Date: 2004-08-24
Classification: G01N

Abstract:
A method of screening a xenobiotic for susceptibility to biliary excretion, the method comprising the steps of:(a) establishing first and second cultures of hepatocytes, each culture comprising at least one bile canaliculus, the first culture having intact bile canaliculi and the second culture having disrupted bile canailculi; (b) exposing a xenobiotic to the first culture and to the second culture for a time (T) sufficient to allow uptake of the xenobiotic; (c) washing and then lysing the first and second cultures; (d) measuring an amount of xenobiotic present in a lysate obtained from each culture in step (c); (e) calculating a mass in the bile canaliculi as the difference in the amount of xenobiotic present in the lysates from the first culture having intact bile canaliculi and the second culture having disrupted bile canaliculi; and (f) calculating a biliary clearance value as the ratio of the mass in the bile canaliculi in step (e) and the area under the curve (AUC) in culture medium, wherein the AUC represents the inteqral of xenobiotic concentration in the medium from time 0 to time T, to thereby screen the xenobiotic for susceptibility to biliary excretion.