Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis.
Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interactions, transduction, and homeostatic feedback mechanisms. As the final step, the effects on disease processes and disease progression are considered. Particularly through the incorporation of concepts from receptor theory and dynamical systems analysis, important progress has been made in the field of mechanism-based PK-PD modeling. This has yielded models with much-improved properties for extrapolation and prediction. These models constitute a theoretical basis for rational drug discovery and development.
Danhof
Meindert
M
Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands. m.danhof@lacdr.leidenuniv.nl
de Jongh
Joost
J
De Lange
Elizabeth C M
EC
Della Pasqua
Oscar
O
Ploeger
Bart A
BA
Voskuyl
Rob A
RA
D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D010600:Pharmacology / Q000379:methods*; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D014018:Tissue Distribution
D011956:Receptors, Cell Surface