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      A Metabolomics Approach to Pharmacotherapy Personalization

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          Abstract

          The optimization of drug therapy according to the personal characteristics of patients is a perspective direction in modern medicine. One of the possible ways to achieve such personalization is through the application of “omics” technologies, including current, promising metabolomics methods. This review demonstrates that the analysis of pre-dose metabolite biofluid profiles allows clinicians to predict the effectiveness of a selected drug treatment for a given individual. In the review, it is also shown that the monitoring of post-dose metabolite profiles could allow clinicians to evaluate drug efficiency, the reaction of the host to the treatment, and the outcome of the therapy. A comparative description of pharmacotherapy personalization (pharmacogenomics, pharmacoproteomics, and therapeutic drug monitoring) and personalization based on the analysis of metabolite profiles for biofluids (pharmacometabolomics) is also provided.

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          Innovation: Metabolomics: the apogee of the omics trilogy.

          Gary J Patti, Oscar Yanes, Gary Siuzdak (2012)
          Metabolites, the chemical entities that are transformed during metabolism, provide a functional readout of cellular biochemistry. With emerging technologies in mass spectrometry, thousands of metabolites can now be quantitatively measured from minimal amounts of biological material, which has thereby enabled systems-level analyses. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine.
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            Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.

            J Lazarou, B H Pomeranz, P N Corey (1998)
            To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients. Four electronic databases were searched from 1966 to 1996. Of 153, we selected 39 prospective studies from US hospitals. Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death. The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death. The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.
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              Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy.

              Warwick Dunn, David I. Broadhurst, Helen Atherton … (2011)
              The study of biological systems in a holistic manner (systems biology) is increasingly being viewed as a necessity to provide qualitative and quantitative descriptions of the emergent properties of the complete system. Systems biology performs studies focussed on the complex interactions of system components; emphasising the whole system rather than the individual parts. Many perturbations to mammalian systems (diet, disease, drugs) are multi-factorial and the study of small parts of the system is insufficient to understand the complete phenotypic changes induced. Metabolomics is one functional level tool being employed to investigate the complex interactions of metabolites with other metabolites (metabolism) but also the regulatory role metabolites provide through interaction with genes, transcripts and proteins (e.g. allosteric regulation). Technological developments are the driving force behind advances in scientific knowledge. Recent advances in the two analytical platforms of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have driven forward the discipline of metabolomics. In this critical review, an introduction to metabolites, metabolomes, metabolomics and the role of MS and NMR spectroscopy will be provided. The applications of metabolomics in mammalian systems biology for the study of the health-disease continuum, drug efficacy and toxicity and dietary effects on mammalian health will be reviewed. The current limitations and future goals of metabolomics in systems biology will also be discussed (374 references).
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Pers Med
                Journal ID (iso-abbrev): J Pers Med
                Journal ID (publisher-id): jpm
                Title: Journal of Personalized Medicine
                Publisher: MDPI
                ISSN (Electronic): 2075-4426
                Publication date (Electronic): 05 September 2018
                Publication date Collection: September 2018
                Volume: 8
                Issue: 3
                Electronic Location Identifier: 28
                Affiliations
                Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow 119121, Russia; dlmaslov@ 123456mail.ru (D.L.M.); lokhovpg@ 123456rambler.ru (P.G.L.)
                Author notes
                [* ]Correspondence: balashlen@ 123456mail.ru
                Article
                Publisher ID: jpm-08-00028
                DOI: 10.3390/jpm8030028
                PMC ID: 6164342
                PubMed ID: 30189667
                SO-VID: 350bc978-093c-42a8-a245-7623aff3fe59
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 June 2018
                Date accepted : 03 September 2018
                Categories
                Subject: Review

                Keywords: pharmacometabolomics,metabolomics,pharmacogenomics,therapeutic drug monitoring,personalized medicine,mass spectrometry
                Data availability:
                Keywords: pharmacometabolomics, metabolomics, pharmacogenomics, therapeutic drug monitoring, personalized medicine, mass spectrometry

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