评估代谢酶和转运体变体在依泽替米贝药代动力学中的作用。
Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics.
作者信息
González-Iglesias Eva, Ochoa Dolores, Navares-Gómez Marcos, Zubiaur Pablo, Aldama Marina, de la Torre Tamara, Ríos-Rodríguez Marta de Los, Soria-Chacartegui Paula, Rodríguez-Lopez Andrea, Abad-Santos Francisco, Novalbos Jesús
机构信息
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.
出版信息
Front Pharmacol. 2024 Oct 17;15:1414059. doi: 10.3389/fphar.2024.1414059. eCollection 2024.
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 , , or 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 rs2032582 or rs2273697 and C ( ( ) = 0.056 and 0.087, respectively), which finally reach significance in the multivariate analysis ( ( ) = 0.049 and 0.048, respectively). Nevertheless, these results need to be validated in future studies.
引言
依折麦布通过调节肠道固醇吸收来抑制胆固醇摄取。目前，尽管一些研究已表明由[未提及的某些基因]、[未提及的某些基因]、[未提及的某些基因]或[未提及的某些基因]的改变所导致的依折麦布水平变化，但尚无药物遗传学指南来确认这些生物标志物。本研究的目的是评估22个与代谢和转运相关的药物基因中的49个变体的影响。
方法
对来自四项依折麦布单药治疗或与辛伐他汀联合治疗的生物等效性临床试验的96名健康志愿者进行了研究。采集血样用于未结合依折麦布的血浆定量和基因分型。
结果与讨论
未发现代谢酶变体与依折麦布药代动力学参数之间存在关联。结果显示，对于rs2032582或rs2273697，单变量分析中有一些趋势（分别为C(()) = 0.056和0.087），最终在多变量分析中达到显著水平（分别为C(()) = 0.049和0.048）。然而，这些结果需要在未来的研究中进行验证。
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