Article

Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis.

Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands.
Annual Review of Pharmacology (impact factor: 21.64). 02/2007; 47:357-400. DOI:10.1146/annurev.pharmtox.47.120505.105154 pp.357-400
Source: PubMed

ABSTRACT 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.

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Keywords

activation
 
conventional PK-PD models
 
disease progression
 
drug administration
 
homeostatic feedback mechanisms
 
includes target site distribution
 
mechanism-based PK-PD modeling
 
Mechanism-based PK-PD models
 
much-improved properties
 
quantitative manner
 
rational drug discovery
 
receptor theory
 
theoretical basis
 
transduction