Use of intrinsic clearance for prediction of human hepatic clearance

Importance of the field: The use of intrinsic metabolic stability/clearance and other in vitro pharmacokinetic data for the selection of drug candidates for clinical evaluation during discovery lead optimization has become one of the primary focuses of research organizations involved in new drug discovery. Using intrinsic clearance determined from human liver microsomal preparations and/or hepatocyte to predict human clearance has become more acceptable.Areas covered in this review: This review focuses on the current methods for determining intrinsic clearance and scaling to predict human hepatic clearance, and novel physiologically-based models for improvement of human hepatic clearance prediction. Published microsomal metabolic stability data and in-house hepatocyte clearance data were compared with published in vivo human hepatic clearance data. Various scaling models and the effect of protein binding were examined.What the reader will gain: Use of a novel microfluidic model and other physiologically-b...