Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics.
| Autor: | González-Iglesias E; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Ochoa D; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Navares-Gómez M; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain., Zubiaur P; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Aldama M; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain., de la Torre T; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain., Ríos-Rodríguez ML; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain., Soria-Chacartegui P; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Rodríguez-Lopez A; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Abad-Santos F; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain.; Pharmacology Department, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain., Novalbos J; Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-Princesa), Madrid, Spain. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in pharmacology [Front Pharmacol] 2024 Oct 17; Vol. 15, pp. 1414059. Date of Electronic Publication: 2024 Oct 17 (Print Publication: 2024). |
| DOI: | 10.3389/fphar.2024.1414059 |
| Abstrakt: | Introduction: 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. Methods: 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. Results and Discussion: 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 C Competing Interests: FA-S and DO have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, Cinfa, FAES, Farmal' der, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern, Moderna, MSD, Normon, Novartis, Servier, Silver Pharma, Teva and Zambon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 González-Iglesias, Ochoa, Navares-Gómez, Zubiaur, Aldama, Torre, Ríos-Rodríguez, Soria-Chacartegui, Rodríguez-Lopez, Abad-Santos and Novalbos.) |
| Databáze: | MEDLINE |
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