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Metabolites
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Pharmacometabolomics
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Pharmacometabolomics

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Pharmacology and Drug Metabolism".

Deadline for manuscript submissions: closed (15 December 2019) | Viewed by 16131

Special Issue Editor

Dr. Richard Beger

E-Mail Website
Guest Editor
Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA
Interests: metabolomics; metabonomics; drug toxicity; translational biomarkers; quality control

Special Issue Information

Dear Colleagues,

Pharmacometabolomics or pharmacometabonomics, subsets of the greater metabolomics field, is the study of how differences in metabolites in an individual or subset of the population can be used to predict their varied responses to a drug or medical intervention. At the heart of pharmacometabolomics is the concept that an individual’s metabolic profile is related to their health-to-disease status, which has been referred to as their “metabotype”. Genetics, gender, gut microflora, nutrition, age, health status, or other environmental factors may impact the metabolic profile of an individual. Some of these factors are known to influence the individual response to pharmaceutical compounds. As such, metabolomics profiles obtained prior, during or after a drug or medical intervention can provide predictive, prognostic, and pharmacodynamic response biomarkers to a drug or medical intervention. The pharmacometabolomics data may aid understanding of varied drug responses (i.e. responders vs non-responders), be used to in precision medicine to determine drug dose levels or specific drugs to prescribe for an individual, provide biomarkers related to drug efficacy or toxicity effects and, often simultaneously, provide pharmacokinetics information making pharmacometabolomics valuable for precision medicine. This Special Issue is devoted to the applications of pharmacometabolomics. Topics covered by this Special Issue will include (not exclusively): metabolomics from nonclinical or clinical drug studies, pharmacometabolomics studies that can differentiate gender or racial differences in a drug response, precision medicine studies that combine pharmacometabolomics with pharmacogenomics data, and pharmacometabolomics studies that include pharmacokinetics (PK) and pharmacodynamics (PD) information.

Dr. Richard Beger
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Personalized medicine
  • Biomarkers
  • Pharmacometabolomics
  • Pharmacokinetics
  • Pharmacodynamics
  • Precision medicine
  • Metabolic profile
  • Metabolomics

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Published Papers (3 papers)

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Research

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26 pages, 3722 KiB  
Article
Dexamethasone-Induced Perturbations in Tissue Metabolomics Revealed by Chemical Isotope Labeling LC-MS Analysis
by Lina A. Dahabiyeh, Abeer K. Malkawi, Xiaohang Wang, Dilek Colak, Ahmed H. Mujamammi, Essa M. Sabi, Liang Li, Majed Dasouki and Anas M. Abdel Rahman
Metabolites 2020, 10(2), 42; https://doi.org/10.3390/metabo10020042 - 21 Jan 2020
Cited by 29 | Viewed by 5425
Abstract
Dexamethasone (Dex) is a synthetic glucocorticoid (GC) drug commonly used clinically for the treatment of several inflammatory and immune-mediated diseases. Despite its broad range of indications, the long-term use of Dex is known to be associated with specific abnormalities in several tissues and [...] Read more.
Dexamethasone (Dex) is a synthetic glucocorticoid (GC) drug commonly used clinically for the treatment of several inflammatory and immune-mediated diseases. Despite its broad range of indications, the long-term use of Dex is known to be associated with specific abnormalities in several tissues and organs. In this study, the metabolomic effects on five different organs induced by the chronic administration of Dex in the Sprague–Dawley rat model were investigated using the chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS) platform, which targets the amine/phenol submetabolomes. Compared to controls, a prolonged intake of Dex resulted in significant perturbations in the levels of 492, 442, 300, 186, and 105 metabolites in the brain, skeletal muscle, liver, kidney, and heart tissues, respectively. The positively identified metabolites were mapped to diverse molecular pathways in different organs. In the brain, perturbations in protein biosynthesis, amino acid metabolism, and monoamine neurotransmitter synthesis were identified, while in the heart, pyrimidine metabolism and branched amino acid biosynthesis were the most significantly impaired pathways. In the kidney, several amino acid pathways were dysregulated, which reflected impairments in several biological functions, including gluconeogenesis and ureagenesis. Beta-alanine metabolism and uridine homeostasis were profoundly affected in liver tissues, whereas alterations of glutathione, arginine, glutamine, and nitrogen metabolism pointed to the modulation of muscle metabolism and disturbances in energy production and muscle mass in skeletal muscle. The differential expression of multiple dipeptides was most significant in the liver (down-regulated), brain (up-regulation), and kidney tissues, but not in the heart or skeletal muscle tissues. The identification of clinically relevant pathways provides holistic insights into the tissue molecular responses induced by Dex and understanding of the underlying mechanisms associated with their side effects. Our data suggest a potential role for glutathione supplementation and dipeptide modulators as novel therapeutic interventions to mitigate the side effects induced by Dex therapy. Full article
(This article belongs to the Special Issue Pharmacometabolomics)
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11 pages, 2933 KiB  
Article
Pharmacometabolomic Pathway Response of Effective Anticancer Agents on Different Diets in Rats with Induced Mammary Tumors
by Zhijun Cao, Mark Steven Miller, Ronald A. Lubet, Clinton J. Grubbs and Richard D. Beger
Metabolites 2019, 9(7), 149; https://doi.org/10.3390/metabo9070149 - 22 Jul 2019
Cited by 4 | Viewed by 3134
Abstract
Metabolomics is an effective approach to characterize the metabotype which can reflect the influence of genetics, physiological status, and environmental factors such as drug intakes, diet. Diet may change the chemopreventive efficacy of given agents due to the altered physiological status of the [...] Read more.
Metabolomics is an effective approach to characterize the metabotype which can reflect the influence of genetics, physiological status, and environmental factors such as drug intakes, diet. Diet may change the chemopreventive efficacy of given agents due to the altered physiological status of the subject. Here, metabolomics response to a chemopreventive agent targretin or tamoxifen, in rats with methylnitrosourea-induced tumors on a standard diet (4% fat, CD) or a high fat diet (21% fat, HFD) was evaluated, and found that (1) the metabolome was substantially affected by diet and/or drug treatment; (2) multiple metabolites were identified as potential pharmacodynamic biomarkers related to targretin or tamoxifen regardless of diet and time; and (3) the primary bile acid pathway was significantly affected by targretin treatment in rats on both diets, and the lysolipid pathway was significantly affected by tamoxifen treatment in rats on the high fat diet. Full article
(This article belongs to the Special Issue Pharmacometabolomics)
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Review

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19 pages, 1369 KiB  
Review
Current Concepts in Pharmacometabolomics, Biomarker Discovery, and Precision Medicine
by Richard D. Beger, Michael A Schmidt and Rima Kaddurah-Daouk
Metabolites 2020, 10(4), 129; https://doi.org/10.3390/metabo10040129 - 27 Mar 2020
Cited by 61 | Viewed by 5832
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Pharmacometabolomics)
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