Hepatobiliary Dispostion and Drug Transport
Prediction of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR® (sandwich-cultured hepatocytes) is an in vitro system that is used to analyze and predict the in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance) and transporter-based hepatic drug-drug interactions. When sandwich-cultured hepatocytes are exposed to calcium, junctions remain tight and compound may be retained in both cell and bile. If calcium is not present, junctions open and the contents of the bile pockets are released into the media. Measuring the difference of between these two conditions provides information on uptake and excretion properties of test compound. The HAMILTON Star is able to automate the B-CLEAR® technology in a 24-well format and offers a robust assay.
- Automation of the B-CLEAR® technology in a 24-well format is feasible and offers a robust assay.
- Differences between the automated and manual formats (total accumulation and NSB) have minimal effect on results.
- Throughput is 48 wells per 40 minutes