Predicting the Clearance of CYP2C9 Substrates

Recently, Andersson et al. (2004) reported that quantitative predictions of hepatic clearance from in vitro CL_int values using the “well- stirred liver” model were not useful. Over-prediction of in vivo clearances of four CYP2C9 substrates was found when plasma binding and nonspecific microsomal binding were ignored, and under- prediction when both were accounted for. We have reanalyzed these data showing that reasonably accurate predictions can be obtained in the latter case, when appropriate binding parameters are applied and all metabolic pathways are considered.