Associate Professor Washington State University, Washington
Clinical trials for drug safety and efficacy rarely account for the high inter-individual variability in drug metabolism and transport, thus posing a risk of unpredictable drug safety concerns in populations underrepresented in clinical trials, e.g., women, children, elderly, certain races, etc. Although genetics can predict a fraction of the total variability, non-genetic factors such as age, sex, disease condition, and environmental factors can influence drug metabolism and transport significantly. While cytochrome P450 (CYP) enzymes and some transporters are well characterized for their variability that is often incorporated in physiologically-based pharmacokinetic (PBPK) modeling for predicting drug pharmacokinetics, limited knowledge exists with respect to non-CYP enzymes and proteins involved in disposition of newer drug modalities. Also, the current data on population variability are sparse and don’t address technical variability. This presentation will focus on i) building a knowledge base of robust quantitative proteomics data of drug target proteins for utilization in PBPK modeling, and ii) developing non-invasive approaches (biomarkers and liquid biopsy) for characterizing drug disposition related variability, using state-of-the-art quantitative mass spectroscopy.
Learning Objectives:
Understand mechanisms of interindividual variability in drug pharamcokinetics.
Appreciate the applications of quantomics proteomics and metabolomics in translational pharmacology.
Understand basics of proteomics-informaed physiologically based pharmacokinetic modeling
Apply quantitative omics tools in translational pharamcology