What is B-CLEAR®?
The B-CLEAR® technology refers to a patented methodology that, when applied to properly functioning hepatocytes in culture, opens the bile pockets (analogous to bile canaliculi in vivo), allowing the measurement of material that has been transported from inside the cell. Measurement of biliary efflux allows us to exclusively evaluate biliary clearance and biliary transporter interactions, as well as perform cellular mass balance measurements. The three main B-CLEAR® technology platforms are patented in 45 countries worldwide.
Data from the B-CLEAR® model has been used in a variety of ways including in the prediction of clinically relevant drug interactions and in regulatory submissions to the FDA in support of mechanisms of transporter interactions and hepatotoxicity.
What is an integrated hepatic model and why is it important?
An integrated in vitro model maintains physiologic cellular components and processes at in vivo-relevant amounts. In the sandwich-cultured hepatocyte model, relevant drug transporter proteins (uptake and efflux), as well as drug metabolizing enzymes (Phase I and II), are expressed, maintained, and functioning together in the same system. The figure below graphically represents this concept.
To obtain a true in vivo understanding of hepatic disposition and drug interactions, all three major clearance pathways (uptake, metabolism, and efflux) must be present, ideally, within the same model system. A system that integrates these three pathways together can assess cellular compensation effects, which mirrors the in vivo situation. In addition, the presence of functional clearance pathways together means that studies to assess induction, hepatotoxicity, cholestasis, clearance, or drug interactions automatically generate physiologic concentrations and metabolites, thereby removing the need to artificially estimate or guess appropriate intracellular concentrations or conditions.