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托莫西汀药物遗传学:与药代动力学、治疗反应及耐受性的关联

Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.

作者信息

Brown Jacob T, Bishop Jeffrey R

机构信息

Department of Pharmacy Practice & Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN 55802, USA.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

Pharmacogenomics. 2015;16(13):1513-20. doi: 10.2217/PGS.15.93. Epub 2015 Aug 28.

Abstract

Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder and is predominantly metabolized by the CYP2D6 enzyme. Differences in pharmacokinetic parameters as well as clinical treatment outcomes across CYP2D6 genotype groups have resulted in dosing recommendations within the product label, but clinical studies supporting the use of genotype guided dosing are currently lacking. Furthermore, pharmacokinetic and clinical studies have primarily focused on extensive as compared with poor metabolizers, with little information known about other metabolizer categories as well as genes involved in the pharmacodynamics of atomoxetine. This review describes the pharmacogenetic associations with atomoxetine pharmacokinetics, treatment response and tolerability with considerations for the clinical utility of this information.

摘要

托莫西汀适用于治疗注意力缺陷多动障碍,主要通过CYP2D6酶代谢。CYP2D6基因型组之间的药代动力学参数以及临床治疗结果存在差异,这导致了产品标签中的给药建议,但目前缺乏支持使用基因型指导给药的临床研究。此外,与慢代谢者相比,药代动力学和临床研究主要集中在快代谢者身上,关于其他代谢者类别以及参与托莫西汀药效学的基因的信息知之甚少。本综述描述了托莫西汀药代动力学、治疗反应和耐受性的药物遗传学关联,并考虑了该信息的临床实用性。

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