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Article Dans Une Revue Clinical and Translational Science. Année : 2023

Plasma lipidomic analysis to investigate putative biomarkers of P-glycoprotein activity in healthy volunteers

Résumé

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 similar to 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 similar to 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.
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hal-04191159 , version 1 (25-09-2023)

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Paternité - Pas d'utilisation commerciale

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Theodore Decaix, Romain Magny, Isabelle Gouin-Thibaut, Xavier Delavenne, Patrick Mismetti, et al.. Plasma lipidomic analysis to investigate putative biomarkers of P-glycoprotein activity in healthy volunteers. Clinical and Translational Science., 2023, ⟨10.1111/cts.13601⟩. ⟨hal-04191159⟩
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