Predicting carrier-mediated hepatic disposition of rosuvastatin in man by scaling from individual transfected cell-lines in vitro using absolute transporter protein quantification and PBPK modeling.

In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...

Physiologically based pharmacokinetic modeling of cyclohexane as a tool for integrating animal and human test data

This report describes a physiologically based pharmacokinetic model for cyclohexane and its use in comparing internal doses in rats and volunteers following inhalation exposures. Parameters describing saturable metabolism of cyclohexane are measured in rats and used along with experimentally determined partition coefficients. The model is...

Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the...