Brown Jacob T
Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, College of Pharmacy, Duluth, MN, USA.
Methods Mol Biol. 2022;2547:427-436. doi: 10.1007/978-1-0716-2573-6_15.
ADHD is a common condition in both children and adults. The most prescribed medications for the treatment of ADHD include methylphenidate, mixed amphetamine salts, atomoxetine, guanfacine, and clonidine. While each of these medications have their own distinct pharmacokinetic profile, the extent to which pharmacogenetics effects their pharmacokinetic parameters is best described in atomoxetine, followed by methylphenidate. Atomoxetine is predominantly metabolized by cytochrome p450 2D6 (CYP2D6), while methylphenidate is metabolized by carboxylesterase 1 (CES1). Both CYP2D6 and CES1 have multiple variants resulting in varying levels of enzyme activity; however, to date, the functional consequence of variants and alleles for CYP2D6 is better characterized as compared to CES1. Regarding CYP2D6, individuals who are poor metabolizers prescribed atomoxetine experience up to ten-fold higher exposure as compared to normal metabolizers at comparable dosing. Additionally, individuals prescribed methylphenidate with the rs71647871 variant may experience up to 2.5-fold higher exposure as compared to those without. Having this pharmacogenetic information available may aid clinicians and patients when choosing medications and doses to treat ADHD.
注意缺陷多动障碍（ADHD）在儿童和成人中都很常见。治疗ADHD最常用的药物包括哌醋甲酯、复方苯丙胺盐、托莫西汀、胍法辛和可乐定。虽然这些药物各自都有独特的药代动力学特征，但药物遗传学对其药代动力学参数的影响程度在托莫西汀中描述得最为详细，其次是哌醋甲酯。托莫西汀主要由细胞色素P450 2D6（CYP2D6）代谢，而哌醋甲酯由羧酸酯酶1（CES1）代谢。CYP2D6和CES1都有多个变体，导致酶活性水平不同；然而，迄今为止，与CES1相比，CYP2D6变体和等位基因的功能后果得到了更好的表征。关于CYP2D6，服用托莫西汀的慢代谢者在同等剂量下的暴露量比正常代谢者高出多达10倍。此外，服用具有rs71647871变体的哌醋甲酯的个体与没有该变体的个体相比，暴露量可能高出多达2.5倍。掌握这些药物遗传学信息可能有助于临床医生和患者选择治疗ADHD的药物和剂量。
