Abstract: Methods of screening a compound for susceptibility to causing systemic or hepatic toxicity, using a hepatic cell system exposed to a range of concentrations of a bile acid in the absence or presence of a compound to determine a toxicity profile. In vitro systems for predicting in vivo hepatotoxic potential of a compound are also provided, and include in vitro cultured hepatic cell systems with a capacity for bile acid synthesis, bile acid transport and bile acid regulation.

Abstract: A method of evaluating disposition and/or effect of a candidate compound in an in vitro culture and/or suspension to predict in vivo disposition and/or effect of the candidate compound, which can include the steps of providing a cell culture and/or suspension; exposing a candidate compound to the culture and/or suspension; exposing the culture and/or suspension to a media providing an in vivo relevant extracellular environment, such as a media comprising a component (such as a protein and/or other component, such as lipoproteins, bile acids, and endogenous compounds such as bilirubin) at a physiologic concentration or a concentration having characteristics, such as binding characteristics, similar to the physiological concentration; wherein any combination of any of the exposing steps can occur in any order or simultaneously; and evaluating in vitro disposition and/or effect of the compound to predict in vivo disposition and/or effect of the candidate compound.