Accumulation of Taurocholic Acid in B-CLEAR® Human Sandwich-Cultured Hepatocytes in the Presence of Clinically Relevant Cholestatic Agents
Drug induced liver injury (DILI) has led to the withdrawal of drugs from the market. One postulated mechanism of DILI is cholestasis caused by inhibition of the bile salt efflux pump (BSEP). Inhibition of BSEP can be measured in vitro with BSEP expressing vesicles. However, not all drugs identified as BSEP inhibitors cause DILI as there are many pathways involved in cholestatic toxicity. An in vitro system which models in vivo transporter expression and functionality more completely may better predict the potential of drugs to cause cholestasis or DILI. We evaluated the hepatobiliary disposition of taurocholic acid (TCA) in the presence of cholestatic agents using B-CLEAR®human sandwich-cultured hepatocytes.