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Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers
P‐glycoprotein (P‐gp) is an efflux transporter involved in the bioavailability of many drugs currently on the market. P‐gp is responsible for several drug–drug interactions encountered in clinical practice leading to iatrogenic hospital admissions, especially in polypharmacy situations. ABCB1 genoty...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582668/ https://www.ncbi.nlm.nih.gov/pubmed/37529981 http://dx.doi.org/10.1111/cts.13601 |
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author | Decaix, Théodore Magny, Romain Gouin‐Thibaut, Isabelle Delavenne, Xavier Mismetti, Patrick Salem, Joe‐Elie Narjoz, Céline Blanchard, Anne Pépin, Marion Auzeil, Nicolas Loriot, Marie‐Anne Laprévote, Olivier |
author_facet | Decaix, Théodore Magny, Romain Gouin‐Thibaut, Isabelle Delavenne, Xavier Mismetti, Patrick Salem, Joe‐Elie Narjoz, Céline Blanchard, Anne Pépin, Marion Auzeil, Nicolas Loriot, Marie‐Anne Laprévote, Olivier |
author_sort | Decaix, Théodore |
collection | PubMed |
description | P‐glycoprotein (P‐gp) is an efflux transporter involved in the bioavailability of many drugs currently on the market. P‐gp is responsible for several drug–drug interactions encountered in clinical practice leading to iatrogenic hospital admissions, especially in polypharmacy situations. ABCB1 genotyping only reflects an indirect estimate of P‐gp activity. Therefore, it would be useful to identify endogenous biomarkers to determine the P‐gp phenotype to predict in vivo activity prior to the initiation of treatment and to assess the effects of drugs on P‐gp activity. The objective of this study was to assess changes in plasma lipidome composition among healthy volunteers selected on the basis of their ABCB1 genotype and who received clarithromycin, a known inhibitor of P‐gp. Untargeted lipidomic analysis based on liquid chromatography–tandem mass spectrometry was performed before and after clarithromycin administration. Our results revealed changes in plasma levels of some ceramides (Cers) {Cer(d18:1/22:0), Cer(d18:1/22:1), and Cer(d18:1/20:0) by ~38% (p < 0.0001), 13% (p < 0.0001), and 13% (p < 0.0001), respectively} and phosphatidylcholines (PCs) {PC(17:0/14:1), PC(16:0/18:3), and PC(14:0/18:3) by ~24% (p < 0.001), 10% (p < 0.001), and 23.6% (p < 0.001)} associated with both ABCB1 genotype and clarithromycin intake. Through the examination of plasma lipids, our results highlight the relevance of untargeted lipidomics for studying in vivo P‐gp activity and, more generally, to safely phenotyping transporters. |
format | Online Article Text |
id | pubmed-10582668 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105826682023-10-19 Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers Decaix, Théodore Magny, Romain Gouin‐Thibaut, Isabelle Delavenne, Xavier Mismetti, Patrick Salem, Joe‐Elie Narjoz, Céline Blanchard, Anne Pépin, Marion Auzeil, Nicolas Loriot, Marie‐Anne Laprévote, Olivier Clin Transl Sci Research P‐glycoprotein (P‐gp) is an efflux transporter involved in the bioavailability of many drugs currently on the market. P‐gp is responsible for several drug–drug interactions encountered in clinical practice leading to iatrogenic hospital admissions, especially in polypharmacy situations. ABCB1 genotyping only reflects an indirect estimate of P‐gp activity. Therefore, it would be useful to identify endogenous biomarkers to determine the P‐gp phenotype to predict in vivo activity prior to the initiation of treatment and to assess the effects of drugs on P‐gp activity. The objective of this study was to assess changes in plasma lipidome composition among healthy volunteers selected on the basis of their ABCB1 genotype and who received clarithromycin, a known inhibitor of P‐gp. Untargeted lipidomic analysis based on liquid chromatography–tandem mass spectrometry was performed before and after clarithromycin administration. Our results revealed changes in plasma levels of some ceramides (Cers) {Cer(d18:1/22:0), Cer(d18:1/22:1), and Cer(d18:1/20:0) by ~38% (p < 0.0001), 13% (p < 0.0001), and 13% (p < 0.0001), respectively} and phosphatidylcholines (PCs) {PC(17:0/14:1), PC(16:0/18:3), and PC(14:0/18:3) by ~24% (p < 0.001), 10% (p < 0.001), and 23.6% (p < 0.001)} associated with both ABCB1 genotype and clarithromycin intake. Through the examination of plasma lipids, our results highlight the relevance of untargeted lipidomics for studying in vivo P‐gp activity and, more generally, to safely phenotyping transporters. John Wiley and Sons Inc. 2023-08-02 /pmc/articles/PMC10582668/ /pubmed/37529981 http://dx.doi.org/10.1111/cts.13601 Text en © 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Decaix, Théodore Magny, Romain Gouin‐Thibaut, Isabelle Delavenne, Xavier Mismetti, Patrick Salem, Joe‐Elie Narjoz, Céline Blanchard, Anne Pépin, Marion Auzeil, Nicolas Loriot, Marie‐Anne Laprévote, Olivier Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title | Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title_full | Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title_fullStr | Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title_full_unstemmed | Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title_short | Plasma lipidomic analysis to investigate putative biomarkers of P‐glycoprotein activity in healthy volunteers |
title_sort | plasma lipidomic analysis to investigate putative biomarkers of p‐glycoprotein activity in healthy volunteers |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10582668/ https://www.ncbi.nlm.nih.gov/pubmed/37529981 http://dx.doi.org/10.1111/cts.13601 |
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