In vitro prediction of in vivo hepatic metabolic clearance of drugs in human
HE Zhong-gui · Chinese Journal of New Drugs and Clinical Remedies · 2007
It is of great importance to identify the new chemical entity (NCE) with poor pharmacokinetic properties early in drug discovery pipeline.In vitro prediction of in vivo hepatic metabolic clearance of compounds in human can be used to screen those compounds that are likely to be eliminated too quickly from the body and,therefore,to establish models for predicting oral bioavailability and to direct the clinical dosage regimen.This review presents a strategy to achieve the prediction of in vivo human hepatic clearance of drugs from in vitro systems such as hepatic microsomes and hepatocytes.The potential role of plasma and matrix protein binding in accurate clearance prediction is also discussed.