Intersystem extrapolation factor

Ho vever this approach does not address inter-individual variability in CYP expression nor the apparent substrate specificity of RAFs. This may be overcome through the use of intersystem extrapolation factors (ISEFs) vhich compare the intrinsic activities of rCYP versus liver microsomes and provide CYP abundance scaling by mathematical means. This employs the RAF approach and adjusts for the actual amount of liver microsomes CYP present (measured by immunochemistry) rather than a theoretical amount (Equation 8.4). Such corrections can be made using nominal specific contents of individual CYP proteins in liver microsomes or more appropriately employ modeling and simulation software (e.g., SIMCYP www.simcyp.com) which takes into account population-based variability in CYP content. 

Proctor, N.J., Tucker, G.T. and Rostami-Hodjegan, A. (2004) Predicting drug clearance from recombinantly expressed CYPs intersystem extrapolation factors. Xenobiotica, 34, 151-178. 

Another approach that has been used to correct for differences in microsomes isolated from human livers versus individual enzymes expressed in heterologous expression systems involves the application of intersystem extrapolation factors, or ISEFs, that are empirically derived correction factors. 

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