Can you use hepatocyte rather than microsomal intrinsic clearance data in Cloe® PK?
A. It is possible to use hepatocyte clearance as an alternative, although you should exercise some caution in interpreting the results. In the current version (v2.1) of Cloe® PK, we recommend using microsomal, rather than hepatocyte, clearance for the following reasons: 1. Transport across the hepatocyte plasma membrane, and metabolism within the hepatocyte are explicitly modelled as two separate processes within Cloe® PK, whereas the rates of these processes cannot be distinguished from one another with a standard hepatocyte clearance assay. 2. Hepatocyte and microsomal clearance data do not always scale equally well, for reasons that are not always clear. Therefore, we did not want to equate microsomal and hepatocyte metabolic clearance until the relationship between them is more quantifiable. Note that we have not done any work to validate the reliability of predictions using hepatocyte data in this version of Cloe® PK.
