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Intersubject and Intrasubject Variability of Potential Plasma and Urine Metabolite and Protein Biomarkers in Healthy Human Volunteers
Author(s) -
Duisters Kevin,
Ogino Shinji,
Andou Tomohiro,
Ito Kazumi,
Akabane Takafumi,
Harms Amy,
Moerland Matthijs,
Hashimoto Yuka,
Ando Ayumi,
Ohtsu Yoshiaki,
Wada Naoya,
Yukinaga Hideo,
Meulman Jacqueline,
Kobayashi Hiroyuki,
Kobayashi Nobuhiro,
Suzumura Kenichi,
Hankemeier Thomas
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1606
Subject(s) - metabolite , urine , in vivo , biomarker , chemistry , pharmacology , medicine , biology , biochemistry , microbiology and biotechnology
A limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro / in vivo studies to clinical trials and clinical decision support. Specifically, variability of biomolecule concentration can play an important role in interpretation, power analysis, and sampling time designation. In the present study, a wide range of 749 plasma metabolites, 62 urine biogenic amines, and 1,263 plasma proteins were analyzed in 10 healthy male volunteers measured repeatedly during 12 hours under tightly controlled conditions. Three variability components in relative concentration data are determined using linear mixed models: between (intersubject), time (intrasubject), and noise (intrasubject). Biomolecules such as 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoate, platelet‐derived growth factor C, and cathepsin D with low noise potentially detect changing conditions within a person. If also the between component is low, biomolecules can easier differentiate conditions between persons, for example cathepsin D, CD 27 antigen, and prolylglycine. Variability over time does not necessarily inhibit translatability, but requires choosing sampling times carefully.