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.
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.