One-compartment (1C) and permeability-limited models were used to evaluate the ability of
microsomal and hepatocyte intrinsic clearances to predict hepatic clearance. Well-stirred …

Understanding the extended clearance concept and establishing a physiologically based
pharmacokinetic (PBPK) model are crucial for investigating the impact of changes in …

In recent years, there has been a large expansion in both the range and use of in vitro
systems to study drug metabolism and metabolism-related phenomena. Purified enzymes …

It has been well accepted that hepatic drug extraction depends on the blood flow, vascular
binding, transmembrane barriers, transporters, enzymes and cosubstrate and their zonal …

In the development of new drugs, the prediction of metabolite‐to‐parent plasma exposure
ratio in humans prior to administration in a clinical study has emerged as an important need …

Recent studies of membrane transporters have revealed their importance in determining the
pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic …

Accurately predicting hepatic clearance is an integral part of the drug-development process,
and yet current in vitro to in vivo (IVIVE) extrapolation methods yield poor predictions …

Hepatic clearance (CLH) prediction is a critical parameter to estimate human dose.
However, CLH underpredictions are common, especially for slowly metabolized drugs, and …

Both metabolizing enzymes and drug transporters play important roles in modulating drug
absorption, distribution, metabolism and elimination. Acting alone or in concert with each …

Previously in vitro–in vivo extrapolation (IVIVE) with the Simcyp Clearance and Interaction
Simulator® has been used to predict the clearance of 15 clinically used drugs in humans …