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10.1208/s12248-014-9690-8 http://scihub22266oqcxt.onion/10.1208/s12248-014-9690-8 25445845QuantitativePredictionofHumanPharmacokineticsformAbsExhibitingTarget-MediatedDisposition.!4365083!25445845     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       AAPS+J 2015 ; 17 (2): 389-99 Nephropedia Template TP {{tp|p=25445845|t=2015. Quantitative prediction of human pharmacokinetics for mAbs exhibiting target-mediated disposition |pdf=|usr=}}{{25445845}} gab.com Text Quantitative prediction of human pharmacokinetics for mAbs exhibiting target-mediated disposition JO: AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=25445845 #FOAvip Prediction of human pharmacokinetics (PK) can be challenging for monoclonal antibodies (mAbs) exhibiting target-mediated drug disposition (TMDD). In this study, we performed a quantitative analysis of a diverse set of six mAbs exhibiting TMDD to explore translational rules that can be utilized to predict human PK. A TMDD model with rapid-binding approximation was utilized to fit PK and PD (i.e., free and/or total target levels) data, and average absolute fold error (AAFE) was calculated for each model parameter. Based on the comparative analysis, translational rules were developed and applied to a test antibody not included in the original analysis. AAFE of less than two-fold was observed between monkey and human for baseline target levels (R 0), body-weight (BW) normalized central elimination rate (K el/BW(-0.25)) and central volume (V c/BW(1.0)). AAFE of less than three-fold was estimated for the binding affinity constant (K D). The other four parameters, i.e., complex turnover rate (K int), target turnover rate (K deg), central to peripheral distribution rate constant (K pt) and peripheral to central rate constant (K tp) were poorly correlated between monkey and human. The projected human PK of test antibody based on the translation rules was in good agreement with the observed nonlinear PK. In conclusion, we recommend a TMDD model-based prediction approach that integrates in vitro human biomeasures and in vivo preclinical data using translation rules developed in this study. Twit Text FOAVip Quantitative prediction of human pharmacokinetics for mAbs exhibiting target-mediated disposition ????AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=25445845 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25445845 #FOAvip English Wikipedia <ref>{{Cite pmid|25445845}}</ref> Quantitative prediction of human pharmacokinetics for mAbs exhibiting target-mediated disposition #MMPMID25445845 Singh AP; Krzyzanski W; Martin SW; Weber G; Betts A; Ahmad A; Abraham A; Zutshi A; Lin J; Singh P AAPS J 2015[Mar]; 17 (2): 389-99 PMID25445845show ga Prediction of human pharmacokinetics (PK) can be challenging for monoclonal antibodies (mAbs) exhibiting target-mediated drug disposition (TMDD). In this study, we performed a quantitative analysis of a diverse set of six mAbs exhibiting TMDD to explore translational rules that can be utilized to predict human PK. A TMDD model with rapid-binding approximation was utilized to fit PK and PD (i.e., free and/or total target levels) data, and average absolute fold error (AAFE) was calculated for each model parameter. Based on the comparative analysis, translational rules were developed and applied to a test antibody not included in the original analysis. AAFE of less than two-fold was observed between monkey and human for baseline target levels (R 0), body-weight (BW) normalized central elimination rate (K el/BW(-0.25)) and central volume (V c/BW(1.0)). AAFE of less than three-fold was estimated for the binding affinity constant (K D). The other four parameters, i.e., complex turnover rate (K int), target turnover rate (K deg), central to peripheral distribution rate constant (K pt) and peripheral to central rate constant (K tp) were poorly correlated between monkey and human. The projected human PK of test antibody based on the translation rules was in good agreement with the observed nonlinear PK. In conclusion, we recommend a TMDD model-based prediction approach that integrates in vitro human biomeasures and in vivo preclinical data using translation rules developed in this study. |*Models, Biological[MESH] |Animals[MESH] |Antibodies, Monoclonal/*pharmacokinetics[MESH] |Drug Evaluation, Preclinical[MESH] |Humans[MESH] |Macaca fascicularis[MESH] |Nonlinear Dynamics[MESH] |Species Specificity[MESH]Quantitative prediction of human pharmacokinetics for mAbs exhibiting (epmc).pdf DeepDyve Pubget Overpricing