Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.3
4.1
Journals
Metabolites
Special Issues
Metabolomics in Drug Discovery and Development
share announcement

Metabolomics in Drug Discovery and Development

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 September 2021) | Viewed by 6274

Special Issue Editor

Prof. Dr. Ian D Wilson

E-Mail Website
Guest Editor
Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2AZ, UK
Interests: development of hyphenated techniques in chromatography and their application to problems in drug metabolism; toxicology and metabonomics

Special Issue Information

Dear Colleagues,

Metabolomics/metabonomics is now well established as an essential part of the discovery toolbox for understanding complex biochemical processes, as evidenced by the ever-growing number of applications of metabolomics.

One area of application includes the study of xenobiotics, especially drugs, and their effects on endogenous processes as a means of understanding pharmacology and toxicology. This has led to the development of the burgeoning new field of phamacometabonomics/metabolomics, whilst the exploration of toxicity (toxicometabonomics /metabolomics) dates back to the early days of modern metabolic phenotyping. In addition to looking for their effects on the biological system to which they have been applied, the methodologies used for metabolic phenotyping can also be used to search for the drug/xenobiotic metabolites themselves, and there are a number of examples of this type of application. This Special Issue is devoted to compiling the latest research, current practices, and perspectives for using metabolomics holistically for the investigation of drugs. It is therefore not limited to elucidating the effects of drugs on organisms and cell cultures etc., but also includes its application for tracing a drug and its metabolites, from entry into the body to excretion. We also wish to examine applications that investigate the re-emerging role of the gut microbiota in these processes.

We therefore invite primary research articles on the topics of using metabolomics to perform a detailed characterization of drug effects on endogenous metabolism (in biofluids or tissues), the detection of drug metabolites using metabolomic approaches, and explorations of the effect of drugs on the gut microbiota, and of those microorganisms on the drugs themselves.

The Special Issue is open for submissions now. An extension to the submission deadline may be granted if requested in advance. Accepted papers will be published continuously in the journal (as soon as accepted), and will be listed together on the Special Issue website.

Prof. Dr. Ian D Wilson

Guest Editors

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

  • drug metabolism
  • metabolomics
  • toxicology
  • pharmacometabolomics
  • pharmacomicrobiomics
  • molecular networking
  • microbiome
  • xenobiotics

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

16 pages, 2119 KiB  
Article
The Pharmacometabodynamics of Gefitinib after Intravenous Administration to Mice: A Preliminary UPLC–IM–MS Study
by Billy Molloy, Lauren Mullin, Adam King, Lee A. Gethings, Robert S. Plumb and Ian D. Wilson
Metabolites 2021, 11(6), 379; https://doi.org/10.3390/metabo11060379 - 11 Jun 2021
Cited by 5 | Viewed by 2625
Abstract
The effects of intravenous gefitinib (10 mg/kg), an anilinoquinazoline thymidylate kinase inhibitor (TKI), selective for the epidermal growth factor receptor (EGFR), on the urinary metabotypes of mice were studied. We hypothesized that, in response to the administration of gefitinib, there might be significant [...] Read more.
The effects of intravenous gefitinib (10 mg/kg), an anilinoquinazoline thymidylate kinase inhibitor (TKI), selective for the epidermal growth factor receptor (EGFR), on the urinary metabotypes of mice were studied. We hypothesized that, in response to the administration of gefitinib, there might be significant changes in the excretion of many endogenous metabolites in the urine, which could be correlated with the plasma pharmacokinetics (PK) of the drug. In order to investigate this conjecture, urine from male C57 BL6 mice was collected before IV dosing (10 mg/kg) and at 0–3, 3–8, and 8–24 h post-dose. The samples were profiled by UPLC/IM/MS and compared with the profiles obtained from undosed control mice with the data analyzed using multivariate statistical analysis (MVA). This process identified changes in endogenous metabolites over time and these were compared with drug and drug metabolite PK and excretion. While the MVA of these UPLC/IM/MS data did indeed reveal time-related changes for endogenous metabolites that appeared to be linked to drug administration, this analysis did not highlight the presence of either the drug or its metabolites in urine. Endogenous metabolites affected by gefitinib administration were identified by comparison of mass spectral, retention time and ion mobility-derived collision cross section data (compared to authentic standards wherever possible). The changes in endogenous metabolites resulting from gefitinib administration showed both increases (e.g., tryptophan, taurocholic acid, and the dipeptide lysyl-arginine) and decreases (e.g., deoxyguanosine, 8-hydroxydeoxyguanosine, and asparaginyl-histidine) relative to the control animals. By 8–24 h, the post-dose concentrations of most metabolites had returned to near control values. From these studies, we conclude that changes in the amounts of endogenous metabolites excreted in the urine mirrored, to some extent, the plasma pharmacokinetics of the drug. This phenomenon is similar to pharmacodynamics, where the pharmacological effects are related to the drug concentrations, and by analogy, we have termed this effect “pharmacometabodynamics”. Full article
(This article belongs to the Special Issue Metabolomics in Drug Discovery and Development)
►▼ Show Figures

Figure 1

16 pages, 1987 KiB  
Article
Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent
by Tatiana J. Carneiro, Rita Araújo, Martin Vojtek, Salomé Gonçalves-Monteiro, Carmen Diniz, Ana L. M. Batista de Carvalho, M. Paula M. Marques and Ana M. Gil
Metabolites 2021, 11(2), 114; https://doi.org/10.3390/metabo11020114 - 17 Feb 2021
Cited by 10 | Viewed by 2680
Abstract
Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd2Spm) have exhibited particularly beneficial cytotoxic properties, hence [...] Read more.
Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd2Spm) have exhibited particularly beneficial cytotoxic properties, hence unveiling the importance of understanding their impact on organism metabolism. The present study reports the first nuclear magnetic resonance (NMR)-based metabolomics study to assess the in vivo impact of Pd2Spm on the metabolism of healthy mice, to identify metabolic markers with possible relation to biotoxicity/side-effects and their dynamics. The changes in the metabolic profiles of both aqueous and lipophilic extracts of mice kidney, liver, and breast tissues were evaluated, as a function of drug-exposure time, using cisplatin as a reference drug. A putative interpretation was advanced for the metabolic deviations specifically triggered by Pd2Spm, this compound generally inducing faster metabolic response and recovery to control levels for all organs tested, compared to cisplatin (except for kidney lipid metabolism). These results constitute encouraging preliminary metabolic data suggestive of potential lower negative effects of Pd2Spm administration. Full article
(This article belongs to the Special Issue Metabolomics in Drug Discovery and Development)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop