Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1414059
This article is part of the Research Topic Insights in Pharmacogenetics and Pharmacogenomics: 2023 View all 4 articles

Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics

Provisionally accepted
Eva González-Iglesias Eva González-Iglesias 1,2Dolores Ochoa Dolores Ochoa 1,2Marcos Navares-Gómez Marcos Navares-Gómez 1Pablo Zubiaur Pablo Zubiaur 1,2Marina Aldama Marina Aldama 1Tamara De La Torre Tamara De La Torre 1Marta De Los Ríos-Rodríguez Marta De Los Ríos-Rodríguez 1Paula Soria-Chacartegui Paula Soria-Chacartegui 1,2Andrea Rodríguez-Lopez Andrea Rodríguez-Lopez 1,2Francisco Abad-Santos Francisco Abad-Santos 1,2,3*Jesús Novalbos Reina Jesús Novalbos Reina 1*
  • 1 Department of Clinical Pharmacology, Princess University Hospital, Madrid, Spain
  • 2 Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain
  • 3 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain

The final, formatted version of the article will be published soon.

    Ezetimibe inhibits cholesterol uptake by modulation of intestinal sterol absorption. Currently, although some studies have shown alterations in ezetimibe levels caused by alterations in the ABCG5, ABCG8, NPC1L1 or UGT1A1 genes, there are no pharmacogenetic guidelines to confirm these biomarkers. The aim of this work was to evaluate the effect of 49 variants in 22 pharmacogenes related to metabolism and transport. A total of 96 healthy volunteers from four bioequivalence clinical trials of ezetimibe as monotherapy or in combination with simvastatin were studied. Blood samples were extracted for unconjugated ezetimibe plasma quantification and genotyping. No association of metabolizing enzyme variants with ezetimibe pharmacokinetic parameters was found. The results show some trends in the univariate analysis for ABCB1 rs2032582 or ABCC2 rs2273697 and Cmax (p univariate (puv) =0.056 and 0.087, respectively), which finally reach significance in the multivariate analysis (p multivariate (pmv) =0.049 and 0.048, respectively). Nevertheless, these results need to be validated in future studies.

    Keywords: ezetimibe, Simvastatin, Pharmacogenetics, pharmacokinetics, Bioequivalence trials

    Received: 08 Apr 2024; Accepted: 04 Oct 2024.

    Copyright: © 2024 González-Iglesias, Ochoa, Navares-Gómez, Zubiaur, Aldama, De La Torre, De Los Ríos-Rodríguez, Soria-Chacartegui, Rodríguez-Lopez, Abad-Santos and Novalbos Reina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Francisco Abad-Santos, Department of Clinical Pharmacology, Princess University Hospital, Madrid, Spain
    Jesús Novalbos Reina, Department of Clinical Pharmacology, Princess University Hospital, Madrid, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.