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The virtue of translational PKPD modeling in drug discovery: selecting the right clinical candidate while sparing animal lives
Ist Teil von
Drug discovery today, 2013-09, Vol.18 (17-18), p.853-862
Ort / Verlag
England: Elsevier Ltd
Erscheinungsjahr
2013
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
•Implementation of translational PKPD streamlines a discovery screening cascade.•Translational PKPD improves the confidence for selecting the right compound.•Translational PKPD facilitates integration of efficacy and safety signals.•Increased informed decisions in early clinical studies can be made.•Implementation of translational PKPD reduced the use of laboratory animals.
Translational pharmacokinetic–pharmacodynamic (PKPD) modeling has been fully implemented at AstraZeneca's drug discovery unit for central nervous system and pain indications to facilitate timely progression of the right compound to clinical studies, simultaneously assuring essential preclinical efficacy and safety knowledge. This review illustrates the impact of a translational PKPD paradigm with examples from drug discovery programs. Paradoxically, laboratory animal use decreased owing to better understanding of in vitro–in vivo relationships, optimized in vivo study designs, meta-analyses and hypothesis testing using simulations. From an ethical and effectivity perspective, we advocate that translational PKPD approaches should be implemented more broadly in drug discovery.