Narelle K Hansell, Graeme S Halford, Glenda Andrews, David H K Shum, Sarah E Harris, Gail Davies, Sanja Franic, Andrea Christoforou, Brendan Zietsch, Jodie Painter, Sarah E Medland, Erik A Ehli, Gareth E Davies, Vidar M Steen, Astri J Lundervold, Ivar Reinvang, Grant W Montgomery, Thomas Espeseth, Hilleke E Hulshoff Pol, John M Starr, Nicholas G Martin, Stephanie Le Hellard, Dorret I Boomsma, Ian J Deary, Margaret J Wright
Genetic basis of a cognitive complexity metric
PloS one
become apparent recent years need substantial improvement processes used clarify interrelationships compounds pharmacokinetic pk characteristics target actions safety profile particularly challenging techniques currently used obtain meaningful data involve low efficiency animal studies maximize value vivo studies time resources need better utilized one way making major advances adopt integrative approach designing analysing vivo pharmacodynamic pd studies paper address experimental design issues related maximizing information content target engagement refined integration pk pd known quantitative pharmacology pkpd approach advocated enabling clarification interdependence drugs pharmacological properties target physiological systems systemic exposure characteristics several vivo pharmacological case studies presented used illustrate discussion issues experimental design impact rate extent mode administration discussed pharmacological viewpoint examine consequences temporal differences concentration response perspective experimental design also consider importance differences plasma protein binding ppb ability assess pharmacodynamic property safety margin examine usefulness measuring ex vivo ppb finally outline value implementing clearly predetermined integrated work flow generate validate maximize vivo pkpd preclinical disease model data summarize key issues experimental design quantitative pharmacological reasoning focuses concentrationresponse responsetime relationships special emphasis impact drugs disease levy 1993 perspective written raise awareness among vivo scientists pkpd integration essential studies