caa a22 4500 445312165 CHVBK 20180317142634.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0467-9 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0467-9 Systems Pharmacology: Bridging Systems Biology and Pharmacokinetics-Pharmacodynamics (PKPD) in Drug Discovery and Development [Elektronische Daten] [Piet van der Graaf, Neil Benson] 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. Springer Science+Business Media, LLC, 2011 modelling and simulation nationallicence pharmacokinetics/pharmacodynamics nationallicence PKPD nationallicence systems biology nationallicence systems pharmacology nationallicence van der Graaf Piet Pfizer, Department of Pharmacometrics, Global Clinical Pharmacology, IPC 096, CT13 9NJ, Sandwich, UK aut Benson Neil Pfizer Department of Pharmacokinetics, Dynamics & Metabolism (PDM), CT13 9NJ, Sandwich, UK aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1460-1464 0724-8741 28:7<1460 2011 28 11095 https://doi.org/10.1007/s11095-011-0467-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0467-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van der Graaf Piet Pfizer, Department of Pharmacometrics, Global Clinical Pharmacology, IPC 096, CT13 9NJ, Sandwich, UK aut NATIONALLICENCE 700 1- Benson Neil Pfizer Department of Pharmacokinetics, Dynamics & Metabolism (PDM), CT13 9NJ, Sandwich, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1460-1464 0724-8741 28:7<1460 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer