Quantitative mass spectrometry-based proteomics in the era of model-informed drug development: Applications in translational pharmacology and recommendations for best practice

Pharmacology & Therapeutics
Eman El-KhateebBrahim Achour

Abstract

Quantitative translation of the fate and action of a drug in the body is facilitated by models that allow extrapolation of in vitro measurements (such as the rate of metabolism, active transport across membranes, inhibition of enzymes and receptor occupancy) to in vivo consequences (intensity and duration of drug effects). These models use various physiological parameters, including data that describe the expression levels of pharmacologically relevant enzymes, transporters and receptors in tissues and in vitro systems. Immunoquantification approaches have traditionally been used to determine protein expression levels, generally providing relative quantification data with compromised selectivity and reproducibility. More recently, the development of several quantitative proteomic techniques, fuelled by advances in state-of-the-art mass spectrometry, has led to generating a wealth of qualitative and quantitative data. These data are currently used for various quantitative systems pharmacology applications, with the ultimate goal of conducting virtual clinical trials to inform clinical studies, especially when assessments are difficult to conduct on patients. In this review, we explore available quantitative proteomic methods, di...Continue Reading

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Citations

Jan 22, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Narciso CoutoGeoffrey Warhurst
Feb 23, 2020·Annual Review of Analytical Chemistry·Brahim AchourJill Barber
Jun 18, 2020·Frontiers in Cardiovascular Medicine·Deanna BousalisHideko Kasahara
Nov 22, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jonathan RoydsConnail McCrory
Jul 5, 2021·Alimentary Pharmacology & Therapeutics·Eman El-KhateebAmin Rostami-Hodjegan
May 29, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Eman El-KhateebBrahim Achour

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