This modified grant proposal develops methods to address the complexity of modern Pharmacokinetics/Pharmacodynamics (PKPD) population studies focusing on computational PKPD and modeling of complex PKPD systems.
AIM 1, Statistical Estimation Methods for Population PK/PD Data, develops improved estimation methods for population PKPD models, and general methods to incorporate patients compliance behavior and uncertain dosing history into PKPD models.
AIM 2, Modeling System- PKPD, proposes two specific projects modeling system level PKPD across multiple organs, in particular for Cocaine/Nicotine PKPD and addiction dynamics modeling, and drug absorption physiological modeling.
AIM 3, Population Stochastic Differential Equations (SDE), investigates novel approaches to population model building that are based on the use of stochastic differential equation, in particular investigating methodology to include covariates into population PKPD modelsm, and apply SDE to drug-absortion modeling.
This grant proposal develops methods to address the computational and modeling complexity of modern pharmacokinetics and pharmacodynamics (PKPD). We propose novel methodology for Statistical Estimation for Population PK/PD Data, System- PKPD in particular drug addiction and PKPD across multiple organs;investigates novel approaches to population model building that are based on the use of stochastic differential equation;investigate SDE based methodology to build population models including covariates and SDE based deconvolution;develop novel methodology based on Solution Mapping for high dimensional System-PKPD simulation, model reduction and population fitting. We also develop publicly available software implementing our design and model selection methodologies.
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