title: Systems pharmacology: bridging systems biology and pharmacokinetics-pharmacodynamics (PKPD) in drug discovery and development.
abstract: Mechanistic PKPD models are now advocated not only by academic and industrial researchers, but also by regulators. A recent development in this area is based on the growing realisation that innovation could be dramatically catalysed by creating synergy at the interface between Systems Biology and PKPD, two disciplines which until now have largely existed in 'parallel universes' with a limited track record of impactful collaboration. This has led to the emergence of systems pharmacology. Broadly speaking, this is the quantitative analysis of the dynamic interactions between drug(s) and a biological system to understand the behaviour of the system as a whole, as opposed to the behaviour of its individual constituents; thus, it has become the interface between PKPD and systems biology. It applies the concepts of Systems Engineering, Systems Biology, and PKPD to the study of complex biological systems through iteration between computational and/or mathematical modelling and experimentation. Application of systems pharmacology can now impact across all stages of drug research and development, ranging from very early discovery programs to large-scale Phase 3/4 patient studies, and has the potential to become an integral component of a new 'enhanced quantitative drug discovery and development' (EQD3) R&D paradigm.
authors.affiliation: Pfizer, Department of Pharmacometrics, Global Clinical Pharmacology, IPC 096, Sandwich, CT13 9NJ, UK. piet.van.der.graaf@pfizer.com
authors.forename: Piet H
authors.initials: PH
authors.lastname: van der Graaf
authors.forename: Neil
authors.initials: N
authors.lastname: Benson
mesh_terms: D003198:Computer Simulation; D055808:Drug Discovery; D006801:Humans; D008954:Models, Biological; D010600:Pharmacology; D049490:Systems Biology