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Integration of modelling, endogenous biomarkers, and real-world study approaches to support precision dosing in special populations

Application of endogenous biomarkers of drug transporters and liquid biopsy coupled with PBPK modelling to support precision dosing in renal impairment

Monday, November 11, 2024

3:50 PM – 4:15 PM MST

Location: Sonoran Sky Ballroom 5 - 8

Speaker(s)

Aleksandra Galetin, PhD (she/her/hers)

Professor of Translational Pharmacokinetics
University of Manchester
Manchester, England, United Kingdom

Disclosure(s): Abbvie: Grant/Research Support (Ongoing); Bristol Myers Squibb: Grant/Research Support (Ongoing); Eli Lilly and Company: Grant/Research Support (Ongoing); EMD Serono, Merck kGa: Grant/Research Support (Ongoing); Genentech: Grant/Research Support (Ongoing); GSK: Grant/Research Support (Ongoing); Janssen Research & Development: Grant/Research Support (Ongoing); Roche: Employment (Ongoing), Grant/Research Support (Ongoing); Servier: Grant/Research Support (Ongoing); Takeda: Grant/Research Support (Ongoing)

Handouts
Aleksandra Galetin, PhD (she/her/hers)

Professor of Translational Pharmacokinetics
University of Manchester
Manchester, England, United Kingdom

Disclosure(s): Abbvie: Grant/Research Support (Ongoing); Bristol Myers Squibb: Grant/Research Support (Ongoing); Eli Lilly and Company: Grant/Research Support (Ongoing); EMD Serono, Merck kGa: Grant/Research Support (Ongoing); Genentech: Grant/Research Support (Ongoing); GSK: Grant/Research Support (Ongoing); Janssen Research & Development: Grant/Research Support (Ongoing); Roche: Employment (Ongoing), Grant/Research Support (Ongoing); Servier: Grant/Research Support (Ongoing); Takeda: Grant/Research Support (Ongoing)

Handouts

Disclosure(s):

Aleksandra Galetin, PhD: Abbvie: Grant/Research Support (Ongoing); Bristol Myers Squibb: Grant/Research Support (Ongoing); Eli Lilly and Company: Grant/Research Support (Ongoing); EMD Serono, Merck kGa: Grant/Research Support (Ongoing); Genentech: Grant/Research Support (Ongoing); GSK: Grant/Research Support (Ongoing); Janssen Research & Development: Grant/Research Support (Ongoing); Roche: Employment (Ongoing), Grant/Research Support (Ongoing); Servier: Grant/Research Support (Ongoing); Takeda: Grant/Research Support (Ongoing)

Precision dosing strategies require accounting for between-patient variability in pharmacokinetics. To that end, significant progress has been made in identifying and evaluating endogenous biomarkers of transporter function, with a particular focus on the assessment of transporter DDIs and investigation of disease-related changes in transporter function. Recently, tissue-derived plasma exosomes (liquid biopsy) have emerged as a novel tool to quantify changes in expression of enzymes and transporters; a promising link was established between exosomes and tissue expression of key ADME proteins. These endogenous biomarkers hold the most promising position to support to uncover the quantitative rules for metabolism enzyme and transporter activities of the pediatrics and geriatrics. But the challenge is how to quantify them accurately since endogenous biomarker turnover rate may change simultaneously. We developed mechanistic PBPK model to capture endogenous biomarker characteristics and accurately predicted the transporter (such as OAT1/3) activities, which will be very helpful for the construction of virtual special populations. The speaker will also summarize the current challenge to uncover enzyme or transporter ontogeny for age-related specific populations and show their perspectives from university side.