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Our support for CYP induction studies includes the following programs:
Our clients rely on our induction study data to guide decision-making through lead selection, clinical study design, regulatory submissions, and response to regulators’ questions. Based on our clients’ research objectives we recommend the following models for induction studies:
We recommend implementing CYP induction studies using TRANSPORTER CERTIFIED™ hepatocytes in sandwich culture for regulatory submissions and most screening studies. This model can show better IVIVE correlations Vs. conventional, transporter-deficient models because it incorporates biliary efflux whereas conventional models do not. Compared to conventional systems, the model better maintains physiologically-relevant intracellular concentrations (ICC) of drug candidates, which is critical for preventing cytotoxicity at the higher concentrations suggested by the FDA. The latest Guidance recommends testing compounds to the limit of solubility or until cytotoxicity is observed. If efflux transporter function is deficient, compounds can accumulate in hepatocytes and cause toxicity. If the hepatocytes have complete transporter function and are able to clear the compound as in vivo, higher concentrations of compound may be tested.
We use HEPATOPAC Technology to create stable hepatocyte cultures that can remain viable for up to 28 days. We recommend HEPATOPAC cultures for compounds that have low uptake and clearance and any experimental design requiring long-term viable hepatocyte cultures. Because of HepatoPac’s extended longevity it is an effective model to investigate long-term CYP enzyme induction or inhibition and has been used for screening studies.