These cell lines transiently express the current FDA and EMA recommended SLC drug transporters (eg. OCT1 and OCT2; OAT1 and OAT3; MATE1; MAT2K…). Conditioned as cryopreserved format, they provide flexibility for experimental planning and can be assayed in just 2 days.
Assessing gene transcription as an endpoint for determining induction of drug metabolizing enzymes and transporters has become the “method of choice” in the FDA’s latest draft Guidance for Industry drug interaction studies. Increased gene transcription due to NCE exposure can be determined by two distinct methods, nuclear receptor activation and changes in mRNA levels in primary hepatocyte cultures.
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 (picture from Qualyst Transporter Solutions). [Read more…]