%0 Journal Article %1 Gabrielsson2009PharmacokineticsLeadCompounds %A Gabrielsson, Johan %A Dolgos, Hugues %A Gillberg, Per-Göran %A Bredberg, Ulf %A Benthem, Bert %A Duker, Göran %D 2009 %J Drug Discovery Today %K drug-design ligand-binding pharmacokinetics residence-times %N 7–8 %P 358 - 372 %R http://dx.doi.org/10.1016/j.drudis.2008.12.011 %T Early integration of pharmacokinetic and dynamic reasoning is essential for optimal development of lead compounds: strategic considerations %U http://www.sciencedirect.com/science/article/pii/S1359644608004431 %V 14 %X The aims of this report are firstly to raise awareness among kineticists and pharmacologists as to why pharmacokinetic–pharmacodynamic (PKPD) integration is essential for target validation (TV), optimizing development of lead compounds (lead generation LG and lead optimization LO) and scaling these to human. A related aim is to demonstrate strategic examples of \PKPD\ collaborations that have improved the planning, execution and evaluation of experiments in primary and safety pharmacology. Examples include design of \TV\ studies, design and data ‘pruning’ of \PKPD\ studies in LO, analysis of data with marginal and substantial temporal (time) differences between exposure and response, design of safety pharmacology studies, assessment of safety margin and assessment of uncertainties in predictions of first dose in human.

@article{Gabrielsson2009PharmacokineticsLeadCompounds, abstract = {The aims of this report are firstly to raise awareness among kineticists and pharmacologists as to why pharmacokinetic–pharmacodynamic (PKPD) integration is essential for target validation (TV), optimizing development of lead compounds (lead generation [LG] and lead optimization [LO]) and scaling these to human. A related aim is to demonstrate strategic examples of \{PKPD\} collaborations that have improved the planning, execution and evaluation of experiments in primary and safety pharmacology. Examples include design of \{TV\} studies, design and data ‘pruning’ of \{PKPD\} studies in LO, analysis of data with marginal and substantial temporal (time) differences between exposure and response, design of safety pharmacology studies, assessment of safety margin and assessment of uncertainties in predictions of first dose in human. }, added-at = {2016-06-04T21:26:10.000+0200}, author = {Gabrielsson, Johan and Dolgos, Hugues and Gillberg, Per-Göran and Bredberg, Ulf and Benthem, Bert and Duker, Göran}, biburl = {https://www.bibsonomy.org/bibtex/2f6778a69ecbcf877573b41586ced202f/salotz}, description = {Early integration of pharmacokinetic and dynamic reasoning is essential for optimal development of lead compounds: strategic considerations}, doi = {http://dx.doi.org/10.1016/j.drudis.2008.12.011}, interhash = {b3557ea93063588b6b205e117bebbd2c}, intrahash = {f6778a69ecbcf877573b41586ced202f}, issn = {1359-6446}, journal = {Drug Discovery Today }, keywords = {drug-design ligand-binding pharmacokinetics residence-times}, number = {7–8}, pages = {358 - 372}, timestamp = {2016-06-04T21:26:10.000+0200}, title = {Early integration of pharmacokinetic and dynamic reasoning is essential for optimal development of lead compounds: strategic considerations }, url = {http://www.sciencedirect.com/science/article/pii/S1359644608004431}, volume = 14, year = 2009 }