New Tools in ADME Prediction: Quantitative Omics, Liquid Biopsies and Modeling

Tuesday April 27, 2021

4:00 pm - 5:30 pm Eastern Time (ET)

View session on the EB Virtual Platform (EB registration required)

BEH DDD DMDD TOX

Chair :

Bhagwat Prasad
Washington State University

Andrew Rowland
Flinders University



Characterization of variability in drug disposition is important for clinical study design and individualized drug treatment. As variability in drug disposition cannot be completely described by genetics, characterization of phenotypic variability is critical. This has fostered the development of plasma-derived exosomes as liquid biopsy and endogenous biomarkers for the prediction of drug metabolism and transport. Integration of metabolomics and proteomics data into physiologically based pharmacokinetic models also supports data translation for better prediction of drug disposition. This symposium will provide an update on various non-invasive and in silico approaches to drive the prediction of in vivo drug disposition.

Speakers

Aleksandra Galetin - University of Manchester

Modelling of Endogenous Transporter Biomarkers to De-risk drug-Drug Interactions in Patients

The presentation will illustrate examples of application of endogenous biomarkers to de-risk perpetrator transporter-mediated interactions and supportive role of modelling and simulation to inform the clinical study design.

Emi Kimoto - Pfizer

Utility of Drug Transporter Proteomics in Support of Translational ADME: Modeling of Transporter-mediated Disposition in Non-alcoholic Steatohepatitis (NASH)

It is now recognized that the expression of various hepatic transporters can be altered by disease (e.g., NASH), which has the potential to impact the pharmacokinetics (PK) of drugs and their drug interaction profiles. Therefore, this presentation will describe the impact of NASH on the expression of the major hepatic transporters and showcase the utility of drug transporter proteomics in support of modeling and simulation-based PK predictions.

Sara Shum - University of Washington

Predicting Renal Clearance of Morphine and Morphine-6-glucuronide using the “Organ-on-a-Chip” Technology and PBPK Modeling 

Kidney tubule-on-a-chip” is a dynamic dual channel 3D microphysiological system (MPS) of human proximal tubule epithelial and endothelial cells that incorporates flow to measure passive diffusion and active secretion clearances. We have demonstrated, using morphine and morphine-6-glucuronide as the model compounds, that the passive diffusion and active secretion clearances measured using the 3D MPS together with a mechanistic kidney PBPK model can be used to reliably predict the renal clearance.  

Andrew Rowland - Flinders University

Exosomes for Prediction of Interindividual Variability in DMEs: How are they Different from Small Molecule Biomarkers?

This presentation will describe the methodologies used to study extracellular vesicle derived markers, the different types of markers and the application of these markers to the prediction of human drug exposure.

Last Updated: February 8, 2021
Key Dates
 
April 27 – 30, 2021

ASPET Annual Meeting at EB 2021

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