We recommend assessing the hepatobiliary disposition of a test article if data from transporter screening study indicates transporter-mediated efflux occurs and if an uptake rate study indicates there is active uptake.
Our novel B-CLEAR study method design enables us to quantitate biliary versus basolateral efflux and so provide an in vitro-relevant estimate of hepatic disposition. Biliary disposition studies are used for the following evaluations of a test article:
- Predict route of hepatic disposition (Biliary Vs. Basolateral).
- Evaluate disposition across species to confirm the validity of in vivo models.
- Compare hepatic disposition of analogs to inform lead selection and optimization decisions.
B-CLEAR Studies using TRANSPROTER CERTIFIED hepatocytes in sandwich culture have physiologically-relevant transporter, metabolism, and regulatory function.
Our hepatobiliary disposition studies include the following deliverables:
- Total Accumulation (Hepatic Uptake)
- Cellular Accumulation (Intracellular Accumulation)
- Hepatic Accumulation (Kp): Ratio of total intracellular concentration to total dose concentration
- Biliary Excretion Index (BEI): (Hepatic Efflux)
- In Vitro Biliary Clearance (Clbiliary): Predictive of in vivo biliary clearance
- Post Incubation Supernatant Concentration (parent and metabolite)
We adapt study protocols based on input from our clients about their test articles and research objectives. Typically, studies include the following assay conditions:
- 3 Concentrations
- 1 Timepoint
- + buffer and – buffer