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抗寄生虫药物遗传反应的视角:一篇综述文章

Perspective on the Genetic Response to Antiparasitics: A Review Article.

作者信息

Alarcon-Valdes Patricia, Ortiz-Reynoso Mariana, Santillan-Benitez Jonnathan

机构信息

Faculty of Chemistry, Autonomous University of the State of Mexico (UAEM), Toluca, México.

出版信息

Iran J Parasitol. 2017 Oct-Dec;12(4):470-481.

Abstract

BACKGROUND

Drugs' pharmacokinetics and pharmacodynamics can be affected by diverse genetic variations, within which simple nucleotide polymorphisms (SNPs) are the most common. Genetic variability is one of the factors that could explain questions like why a given drug does not have the desired effect or why do adverse drug reactions arise.

METHODS

In this retrospective observational study, literature search limits were set within PubMed database as well as the epidemiological bulletins published by the Mexican Ministry of Health, from Jan 1st 2001 to Mar 31st 2017 (16 years).

RESULTS

Metabolism of antiparasitic drugs and their interindividual responses are mainly modified by variations in cytochrome P450 enzymes. These enzymes show high frequencies of polymorphic variability thus affecting the expression of CYP2C, CYP2A, CYP2A6, CYP2D6, CYP2E6 and CYP2A6 isoforms. Research in this field opens the door to new personalized treatment approaches in medicine.

CONCLUSION

Clinical and pharmacological utility yield by applying pharmacogenetics to antiparasitic treatments is not intended as a mean to improve the prescription process, but to select or exclude patients that could present adverse drug reactions as well as to evaluate genetic alterations which result in a diversity of responses, ultimately seeking to provide a more effective and safe treatment; therefore choosing a proper dose for the appropriate patient and the optimal treatment duration. Furthermore, pharmacogenetics assists in the development of vaccines. In other words, the aim of this discipline is to find therapeutic targets allowing personalized treatments.

摘要

背景

药物的药代动力学和药效学可能会受到多种基因变异的影响,其中单核苷酸多态性(SNP)最为常见。基因变异性是解释诸如为什么某种药物没有预期效果或为什么会出现药物不良反应等问题的因素之一。

方法

在这项回顾性观察研究中,检索范围限定于PubMed数据库以及墨西哥卫生部发布的流行病学公告,时间跨度为2001年1月1日至2017年3月31日(共16年)。

结果

抗寄生虫药物的代谢及其个体间反应主要受细胞色素P450酶变异的影响。这些酶表现出高频率的多态性变异,从而影响CYP2C、CYP2A、CYP2A6、CYP2D6、CYP2E6和CYP2A6同工型的表达。该领域的研究为医学上新的个性化治疗方法打开了大门。

结论

将药物遗传学应用于抗寄生虫治疗所产生的临床和药理学效用,并非旨在改善处方过程,而是为了筛选或排除可能出现药物不良反应的患者,以及评估导致反应多样性的基因改变,最终寻求提供更有效、更安全的治疗;因此要为合适的患者选择合适的剂量和最佳的治疗持续时间。此外,药物遗传学有助于疫苗的研发。换句话说,这门学科的目的是找到能够实现个性化治疗的治疗靶点。

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