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patrick-poulin@videotron.ca P. Poulin. April, 2007.Distribution Prediction AAPS – November 11, 2009Validation of Prediction Methods of VdssCurrent initiative of PhRMA/PISC on Predictive ModelsMain focus is on the predictability of human PK based on preclinical data usinga novel and blinded dataset (n=108 drugs).First head-to-head evaluation of models. Publications expected in 2010.PART 1Allometry & OthersCalculation MethodAllometric Wajima(Dedrick)PART 2PhysiologicallyBased (PBPK)Assessment of several methodsused for predicting parametersof ADME (Vdss, CL, AUC, F).Direct validation of 19 differentprediction methods of human Vdss(mechanistic vs. empirical)Assessment of several methods used forpredicting plasma concentration-time profilesby integrating predicted ADME parametersobtained from Part 1.Indirect validation of predictionmethods of Vdss
Additional Validation of this StudyCROSS-VALIDATION OF ALL DISTRIBUTION MODELSPREDICTION METHODSIN VITRO-BASED MODELSTC1 : Poulin & Theil (2002)TC2 : Berezhkovskiy (2004)TC3 : Rodgers & Rowland (2007)TC4 : GastroPlus®Oie-Tozer : Lombardo (2004)Correlation-Hybrid : Poulin & Theil (2009)IN VIVO-BASED MODELSArundel : Astrazeneca (1997)Correlation : Janssen et al. (2008)Literature-based dataThree datasets:A. 39 drugsB. 61 drugsC. 64 drugsLog P (-0.09 to 5)fup: 0.009 to 1pKa 2 to 11ALLOMETRYSA : bound and unbound drugsHuman VdssRat Kp’spatrick-poulin@videotron.ca P. Poulin. April, 2007.Distribution Prediction AAPS – November 11, 2009
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