Prediction of Clearance from Recombinantly Expressed CYPs: Intersystem Extrapolation Factor (ISEF)

Recombinantly expressed human cytochromes P450 (rhCYPs) have been underused for the prediction of human drug clearance (CL). Differences in intrinsic activity (per unit CYP) between rhCYP and human liver enzymes complicate the issue and these discrepancies have not been investigated systematically. We define intersystem extrapolation factors (ISEFs) that allow the use of rhCYP data for … Continued

The Determination of Drug Metabolizing Enzyme Activity In Vivo: Pharmacokinetics and Statistical Issues

Probe substrates for various isoforms of cytochrome P450 and other drug-metabolizing enzymes are now widely used to assess genetic, environmental and ethnic differences in the in vivo metabolism of drugs and other xenobiotics .The key issues in assessing drug-metabolizing enzyme activity in vivo include separation (with the aid of genotyping) of risk and exposure; choice … Continued

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