Leveraging Mathematical Modeling to Quantify Pharmacokinetic and Pharmacodynamic Pathways: Equivalent Dose Metric.

ABSTRACT: Treatment response assays are often summarized by sigmoidal functions comparing cell survival at a single timepoint to applied drug concentration. This approach has a limited biophysical basis, thereby reducing the biological insight gained from such analysis. In particular, drug pharmacokinetic and pharmacodynamic (PK/PD) properties are overlooked in developing treatment response assays, and the accompanying summary statistics conflate these processes. Here, we utilize mathematical modeling to decouple and quantify PK/PD pathways. We experimentally modulate specific pathways with small molecule inhibitors and filter the results with mechanistic mathematical models to obtain quantitative measures of those pathways. Specifically, we investigate the response of cells to time-varying doxorubi

SUBMITTER: McKenna MT 

PROVIDER: S-EPMC6538812 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature