Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine

被引：63

作者：

Beger, Richard D. ^{[1
]}

Schmidt, Michael A. ^{[2
,3
]}

Kaddurah-Daouk, Rima ^{[4
,5
]}

机构：

[1] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA

[2] Adv Pattern Anal & Countermeasures Grp, Boulder, CO 80301 USA

[3] Sovaris Aerosp, Boulder, CO 80301 USA

[4] Duke Univ, Med Ctr, Duke Med, Psychiat & Behav Sci, Box 3903, Durham, NC 27710 USA

[5] Duke Univ, Med Ctr, Duke Inst Brain Sci, Box 3903, Durham, NC 27710 USA

来源：

METABOLITES | 2020年 / 10卷 / 04期

关键词：

pharmacometabolomics; pharmacometabonomics; precision medicine; drug response; metabotypes; GUT MICROBIOTA; DRUG RESPONSE; METFORMIN USE; PHARMACOGENOMICS; VARIABILITY; METABOLOMICS; TOXICITY; THERAPY; ASSOCIATION; DEFICIENCY;

D O I：

10.3390/metabo10040129

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pharmacometabolomics (PMx) studies use information contained in metabolic profiles (or metabolome) to inform about how a subject will respond to drug treatment. Genome, gut microbiome, sex, nutrition, age, stress, health status, and other factors can impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. An individual's metabolic profile has been referred to as his or her "metabotype." As such, metabolomic profiles obtained prior to, during, or after drug treatment could provide insights about drug mechanism of action and variation of response to treatment. Furthermore, there are several types of PMx studies that are used to discover and inform patterns associated with varied drug responses (i.e., responders vs. non-responders; slow or fast metabolizers). The PMx efforts could simultaneously provide information related to an individual's pharmacokinetic response during clinical trials and be used to predict patient response to drugs making pharmacometabolomic clinical research valuable for precision medicine. PMx biomarkers can also be discovered and validated during FDA clinical trials. Using biomarkers during medical development is described in US Law under the 21st Century Cures Act. Information on how to submit biomarkers to the FDA and their context of use is defined herein.

引用

页数：19

共 109 条

[31] Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation [J].

Dethlefsen, Les ;

Relman, David A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 :4554-4561

[32] Pharmacogenetic Labeling of FDA-Approved Drugs A Regulatory Retrospective [J].

Drozda, Katarzyna ;

Pacanowski, Michael A. ;

Grimstein, Christian ;

Zineh, Issam .

JACC-BASIC TO TRANSLATIONAL SCIENCE, 2018, 3 (04) :545-549

[33] Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: The Consortium on Metabonomic Toxicology screening approach [J].

Ebbels, Timothy M. D. ;

Keun, Hector C. ;

Beckonert, Olaf P. ;

Bollard, Mary E. ;

Lindon, John C. ;

Holmes, Elaine ;

Nicholson, Jeremy K. .

JOURNAL OF PROTEOME RESEARCH, 2007, 6 (11) :4407-4422

[34] Pharmacometabolomic signature links simvastatin therapy and insulin resistance [J].

Elbadawi-Sidhu, Mona ;

Baillie, Rebecca A. ;

Zhu, Hongjie ;

Chen, Yii-Der Ida ;

Goodarzi, Mark O. ;

Rotter, Jerome I. ;

Krauss, Ronald M. ;

Fiehn, Oliver ;

Kaddurah-Daouk, Rima .

METABOLOMICS, 2017, 13 (01)

[35] Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability [J].

Ellero-Simatos, S. ;

Lewis, J. P. ;

Georgiades, A. ;

Yerges-Armstrong, L. M. ;

Beitelshees, A. L. ;

Horenstein, R. B. ;

Dane, A. ;

Harms, A. C. ;

Ramaker, R. ;

Vreeken, R. J. ;

Perry, C. G. ;

Zhu, H. ;

Sanchez, C. L. ;

Kuhn, C. ;

Ortel, T. L. ;

Shuldiner, A. R. ;

Hankemeier, T. ;

Kaddurah-Daouk, R. .

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2014, 3 (07)

[36]

Everett JR, 2015, PHARMACOGENOMICS, V16, P737, DOI [10.2217/PGS.15.20, 10.2217/pgs.15.20]

[37] Pharmacometabonomics and personalized medicine [J].

Everett, Jeremy R. ;

Loo, Ruey Leng ;

Pullen, Francis S. .

ANNALS OF CLINICAL BIOCHEMISTRY, 2013, 50 (06) :523-545

[38] Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks [J].

Fearnley, Liam G. ;

Inouye, Michael .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2016, 45 (05) :1319-1328

[39] Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study [J].

Flores, Roberto ;

Shi, Jianxin ;

Fuhrman, Barbara ;

Xu, Xia ;

Veenstra, Timothy D. ;

Gail, Mitchell H. ;

Gajer, Pawel ;

Ravel, Jacques ;

Goedert, James J. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2012, 10

[40] Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients [J].

Frankel, Arthur E. ;

Coughlin, Laura A. ;

Kim, Jiwoong ;

Froehlich, Thomas W. ;

Xie, Yang ;

Frenkel, Eugene P. ;

Koh, Andrew Y. .

NEOPLASIA, 2017, 19 (10) :848-855

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