A method of screening candidate compounds for susceptibility to biliary excretion.

摘要

A method of screening a compound in vitro candidate for susceptibility to biliary excretion in vivo procedure comprising the steps of: each culture comprising at least (a) establishing a first and a second culture of hepatocytes in incubation medium, one canaliculus biliary, wherein the first culture intact bile canaliculi and the second presenting bile canaliculi culture broken; (B) exposing a candidate compound to the first culture and the second culture for a sufficient time (T) to allow incorporation of the candidate compound; (C) washing and then lysing the first and second culture; (D) measuring an amount of candidate compound present in a lysate obtained from each culture in step (c); and (e) calculating a biliary clearance value derived from the first culture having intact bile canaliculi and the second culture having disrupted bile canaliculi using the amount of candidate compound in each lysate decultivo measured in step (d), wherein the biliary clearance is calculated as the amount of compound excreted candidate in the intact bile canaliculi divided by the AUC of the candidate compound in the incubation medium, indicating the value calculated biliary clearance, the candidate compound's susceptibility to biliary excretion in vivo.