PK/PD modelling and beyond: impact on drug development.

PK/PD modelling will play an increasingly important role in drug development, because it will identify key properties of a drug in vivo, allowing the characterization and prediction of the time course of drug effects under physiological and pathological conditions (intensity and duration). It has developed from a descriptive to a mechanism-based approach, taking the relevant processes on the causal path between drug administration and drug effect into account. Recent developments and insights from systems biology and systems pharmacology will provide new information on the complexities of disease associated with the identification of multiple targets for drug treatment.

Pharmacological investigations on lipopolysaccharide-induced permeability changes in the blood-brain barrier in vitro.

Lipopolysaccharide-induced changes in blood-brain barrier (BBB) permeability were investigated with a pharmacological approach in vitro. Lipopolysaccharide induced a concentration- and time-dependent (non)reversible opening of the BBB, and brain astrocytes make brain capillary endothelial cells (BCEC) resistant to this BBB disruption. De novo protein synthesis was essential for the recovery, because cycloheximide prevented the recovery process.