Precision Dosing: 'Liquid Biopsy' Reflects Hepatic Enzyme and Transporter Expression

Activity: Talk or presentationOral presentation

Description

Precision dosing aims to deliver the right drug dose to the right patient based on individual characteristics. In this study, a quantitative link between ‘liquid biopsy’ measurement and liver content of key enzymes and transporters was established to define the metabolic capacity of individual patients. Matched liver tissue and plasma (n=29) were analysed using proteomics and transcriptomics. Plasma expression was normalized using a novel shedding factor, SF, based on 13 liver-specific markers to offset variability in exosomal shedding. Correlation between plasma and liver expression was established; CYPs (r=0.70-0.87, p<0.001), UGTs (r=0.60-0.80, p<0.05), transporters (r=0.66-0.74, p<0.01). ROC analysis demonstrated effective patient stratification (66-88% confidence for slow metabolizers, 77-99% for fast metabolizers). In silico drug trials using CYP3A substrates (midazolam, alprazolam and ibrutinib) via oral route showed similar exposure levels (AUC) with reduced variability by 2-2.5 fold for individualized dosing compared to uniform dosing. This non-invasive technology should facilitate efforts towards better patient stratification and precise drug dose selection. Learning Objectives: >Upon completion, participants should be able to learn about development and validation of 'liquid biopsy' technology. >Upon completion, participants should be able to learn about applications of 'liquid biopsy' technology in: (a) patient stratification, (b) precision dosing and (c) improved enrolment in clinical trials. >Upon completion, participants should be able to learn about the prospective benefits of integration of 'liquid biopsy' in personalized healthcare.
4 Nov 2020

Event (Conference)

TitleAmerican Association of Pharmaceutical Scientists PharmSci 360
Abbrev. TitleAAPS PharmSci 360
Period26/10/205/11/20
Web address (URL)
Location
City
CountryUnited States
Degree of recognitionInternational event