TY - JOUR
T1 - Application of proteomic data in the translation of in vitro observations to associated clinical outcomes
AU - Neuhoff, Sibylle
AU - Harwood, Matthew
AU - Rostami-Hodjegan, Amin
AU - Achour, Brahim
N1 - Funding Information:
The authors would like to thank Dr Ramakrishna Rachumallu (Certara UK Limited, Simcyp Division, Sheffield, UK) and Dr Bhagwat Prasad (Washington State University, Spokane, USA) for assistance with collating data on IVIVE scalars. A.R.-H. and B.A. are grateful for support from the Centre for Applied Pharmacokinetic Research (CAPKR) consortium (Eli Lilly, Takeda, Genentech, AbbVie, Merck, MSD, GSK and Janssen).
Publisher Copyright:
© 2021 The Authors
PY - 2021/6/25
Y1 - 2021/6/25
N2 - Translation of information on drug exposure and effect is facilitated by in silico models that enable extrapolation of in vitro measurements to in vivo clinical outcomes. These models integrate drug-specific data with information describing physiological processes and pathological changes, including alterations to proteins involved in drug absorption, distribution and elimination. Over the past 15 years, quantitative proteomics has contributed a wealth of protein expression data, which are currently used for a variety of systems pharmacology applications, as a complement or a surrogate for activity of the corresponding proteins. In this review, we explore current and emerging applications of targeted and global (untargeted) proteomics in translational pharmacology as well as strategies for improved integration into model-based drug development.
AB - Translation of information on drug exposure and effect is facilitated by in silico models that enable extrapolation of in vitro measurements to in vivo clinical outcomes. These models integrate drug-specific data with information describing physiological processes and pathological changes, including alterations to proteins involved in drug absorption, distribution and elimination. Over the past 15 years, quantitative proteomics has contributed a wealth of protein expression data, which are currently used for a variety of systems pharmacology applications, as a complement or a surrogate for activity of the corresponding proteins. In this review, we explore current and emerging applications of targeted and global (untargeted) proteomics in translational pharmacology as well as strategies for improved integration into model-based drug development.
KW - In vitro-in vivo extrapolation
KW - Physiologically-based pharmacokinetics
KW - Quantitative proteomics
KW - Translational pharmacology
U2 - 10.1016/j.ddtec.2021.06.002
DO - 10.1016/j.ddtec.2021.06.002
M3 - Article
VL - 39
SP - 13
EP - 22
JO - Drug Discovery Today: Technologies
JF - Drug Discovery Today: Technologies
SN - 1740-6749
ER -