1999 Volume 14 Issue supplement Pages 92-93
We have successfully predicted in vivo drug metabolic clearances in human liver from in vitro data obtained using human liver samples. The magnitude of differences between in vivo intrinsic hepatic clearances (CLint, in vivo) and in vitro intrinsic metabolic clearances (CLint, in vitro) calculated from the in vitro metabolic data with human liver microsomes was less than 3-fold for about 60 % of the 50 metabolic reactions catalyzed by cytochrome P450 (CYP). In particular, the predictability was good for those metabolic pathways mediated mainly by CYP3A4. Furthermore, as far as all the 9 metabolic pathways we studied were concerned, the values of CLint, in vitro obtained using recombinant human CYP isozymes were in good agreement with those obtained using human liver microsomes, irrespective of the CYP isozymes involved. This finding suggests that recombinant human CYP isozymes are a good substitute for human liver microsomes as far as predicting in vivo metabolic clearance is concerned.
