We offer the only in vitro model that can quantitate hepatic uptake, intracellular concentration, basolateral and biliary efflux, and biliary clearance. The elimination route of parent compounds and their metabolites, whether basolateral or biliary, is critical to predicting the pharmacokinetics of a compound, its toxicity profile and systemic exposure of metabolites. Our novel “parallel design” method, using B-CLEAR Technology with TRANSPORTER CERTIFIED hepatocytes, enables us to quantitate biliary efflux separately from basolateral efflux and provide an in vivo-relevant estimate of hepatic clearance.
Assessment Programs to Answer Critical Research Questions
Our in vitro hepatobiliary disposition models are used to guide SAR development, understand mechanism of clearance, inform lead selection decisions and clinical program strategies, address regulatory concerns, evaluate transporter-based interactions, and understand the toxicity profile of compounds. We offer customized assessment programs ranging from early screening evaluations, in which we compare and rank analogs and determine if a more in-depth investigation is warranted, to full hepatic clearance studies that predict in vivo outcomes.
Answer Clearance Questions Through the R&D Process
From discovery through regulatory submissions we help our clients answer critical research questions about their compounds:
Does hepatic clearance vary across species?
What is the potential for in vivo hepatic accumulation and biliary clearance?
Which analogs have optimal clearance properties?
Will a compound impact hepatic transporter function?
Is there risk for transporter-based drug-drug interactions?