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ISEFs
Simcyp has developed the use of Intersystem Extrapolation Factors (ISEFs) to convert data obtained using rCYPs to a human liver microsome environment, thereby allowing reliable extrapolation of human drug clearance from these in vitro systems (Proctor et al., 2004; Barter et al., 2006).
ISEFs are calculated by relating the metabolic activity (either intrinsic clearance (CLint) or the Vmax) in your rCYP incubation to that of a representative, characterised pool of human liver microsomes (ideally 20-50 donors).
ISEFs have been defined for many of the commercially available recombinant enzymes (rCYP) and probe substrates, and are provided for the user within the Simcyp substrate databases.
ISEFs were the subject of a Simcyp Focus Group Meeting in April 2006, where members discussed consensus methods for determining ISEFs. A full report of this meeting is available on request.
The Simcyp platform also uses a scaling approach for predicting hepatic, renal and intestinal UGT-mediated metabolism from in vitro recombinant systems.
