Accurate predictions of human pharmacokinetic and pharmacodynamic (PK/PD) profiles are critical in early drug development, as safe, efficacious, and “developable” dosing regimens of promising compounds have to be identified. While advantages of successful integration of preclinical PK/PD data in the “anticipation” of human doses (AHD) have been recognized, pharmaceutical scientists have faced difficulties with practical implementation, especially for PK/PD profile projections of compounds with challenging absorption, distribution, metabolism, excretion and formulation properties. This session will explore:
Practical projection approaches for formulation-dependent human PK/PD parameters and profiles of Biopharmaceutics Classification System classes I-IV drugs based on preclinical data are described
- Case examples for “AHD” demonstrate the utility of preclinical and clinical PK/PD modeling for formulation risk identification, lead candidate differentiation, and prediction of clinical outcome
- Methods to enhance prediction confidence such as in vitro–in vivo extrapolations in clearance predictions using in vitro microsomal data are discussed
- Examples for integration of clinical PK/PD and formulation data from frontrunner compounds via “reverse pharmacology strategies” that minimize uncertainty with PK/PD predictions are included