Method of screening candidate compounds for susceptibility to biliary excretion by endogenous transport systems

A method of screening a xenobiotic in vitro for susceptibility to in vivo biliary excretion by an endogenous sinusoidal or canalicular transport system, or by both sinusoidal and canalicular transport systems, the method comprising the steps of:

• (a) providing a culture of hepatocytes derived from hepatic cells, the culture comprising at least one bile canaliculus;
• (b) simultaneously exposing to the culture provided in step (a), for a time sufficient to allow uptake, both of a xenobiotic and a pre-selected amount of a labeled substrate for an endogenous sinusoidal or canalicular transport system, or for both sinusoidal and canalicular transport systems;
• (c) washing the culture;
• and
• (d) detecting an amount of labeled substrate present in the at least one bile canaliculus in the culture by measuring a signal from the labeled substrate within the at least one bile canaliculus to evaluate uptake and excretion competition between the xenobiotic and the labeled substrate, the presence or the absence of a reduced amount of the labeled substrate as compared to the pre-selected amount of labeled substrate indicating the susceptibility of the xenobiotic to biliary excretion by an endogenous sinusoidal or canalicular transport system, or by both sinusoidal and canalicular transport systems.