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细胞色素 P450 2C19 基因多态性在泮托拉唑代谢及以泮托拉唑为基础的根除方案中的作用。

Role of Genetic Polymorphisms of Cytochrome P450 2C19 in Pantoprazole Metabolism and Pantoprazole-based Eradication Regimens.

机构信息

Faculty of Medicine, Medical Academy, Eiveniu str. 2 LT-50161, Kaunas, Lithuania.

Department of Gastroenterology, Lithuanian Eiveniu str. 2 LT-50161, Kaunas, Lithuania.

出版信息

Curr Drug Metab. 2020;21(11):830-837. doi: 10.2174/1389200221666200514081442.

Abstract

BACKGROUND

Cytochrome P450 (CYP450) enzymes play an important role in the metabolism of 70-80% of the currently used medications, including proton pump inhibitors. There are some data analyzing the impact of gene polymorphisms of CYP450 enzymes on most widely used PPIs, such as omeprazole, however, the data on pantoprazole are highly lacking.

OBJECTIVE

To summarize the most recent publications and studies on the role of polymorphisms of the genes encoding CYP450 enzyme 2C19 in the metabolism of pantoprazole and pantoprazole based Helicobacter pylori eradication regimens.

METHODS

We performed a non-systematic search of the available literature on the selected topic.

RESULTS AND CONCLUSION

The data on cytochrome P450 gene polymorphisms and their role in pantoprazole metabolism and pantoprazole based Helicobacter pylori eradication remain conflicting. Individual differences in pantoprazole metabolism might be partly related to genetic polymorphisms of CYP450 enzymes. Most of the studies support the observation that cytochrome 2C19 polymorphisms have an impact on the pharmacokinetics of pantoprazole and its therapeutic effects: poor metabolizers of PPIs are more likely to have a better response to pantoprazole therapy and achieve better H. pylori eradication rates compared to rapid metabolizers. The determination of alleles that are associated with decreased (e.g., *2, *3 alleles) or increased (e.g., *17 allele) cytochrome 2C19 enzyme activity might be used as predictive factors for the potential of acid suppression and the success of Helicobacter pylori eradication. Overall, currently available data do not provide robust evidence, therefore, the application of genetic polymorphisms of cytochrome enzymes in clinical practice still cannot be recommended as routine practice for personalized pantoprazole prescription strategies.

摘要

背景

细胞色素 P450(CYP450)酶在 70-80%的当前使用药物的代谢中起着重要作用,包括质子泵抑制剂。有一些数据分析 CYP450 酶基因多态性对最广泛使用的质子泵抑制剂(如奥美拉唑)的影响,然而,关于泮托拉唑的数据却非常缺乏。

目的

总结关于编码 CYP450 酶 2C19 的基因多态性在泮托拉唑代谢和基于泮托拉唑的幽门螺杆菌根除方案中的作用的最新出版物和研究。

方法

我们对选定主题的现有文献进行了非系统性搜索。

结果和结论

关于细胞色素 P450 基因多态性及其在泮托拉唑代谢和基于泮托拉唑的幽门螺杆菌根除中的作用的数据仍然存在争议。泮托拉唑代谢的个体差异可能部分与 CYP450 酶的遗传多态性有关。大多数研究支持这样一种观察结果,即细胞色素 2C19 多态性对泮托拉唑的药代动力学和治疗效果有影响:质子泵抑制剂的弱代谢者比快速代谢者更有可能对泮托拉唑治疗有更好的反应,并实现更好的幽门螺杆菌根除率。确定与降低(例如,*2、*3 等位基因)或增加(例如,*17 等位基因)细胞色素 2C19 酶活性相关的等位基因可作为酸抑制潜力和幽门螺杆菌根除成功率的预测因素。总体而言,目前可用的数据并未提供确凿的证据,因此,细胞色素酶遗传多态性在临床实践中的应用仍不能被推荐为个体化泮托拉唑处方策略的常规实践。

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