基因多态性对阿米替林代谢动力学、药效学和不良反应的影响

阿米替林是广泛应用于治疗重症抑郁症和创伤后应激障碍等多种精神疾病的三环类抗抑郁药。但在临床应用过程中发现，阿米替林的药物疗效存在较大个体差异，研究表明，CYP2D6、CYP2C19和ATP结合蛋白亚家族1抗体（ABCB1）等基因的多态性会影响阿米替林的药物代谢动力学(pharmacokinetics,PK)、药效学(pharmacodynamics,PD)和不良反应(adverse reactions,ADR)。在本文中，通过对比CYP2D6和CYP2C19的基因多态性对阿米替林PK、PD和ADR的影响，发现当CYP2C19为快代谢型或正常代谢型时，CYP2D6的基因多态性对阿米替林总体代谢的影响更大，而CYP2C19为慢代谢型时，CYP2C19的基因多态性影响更大。该结论为阿米替林基于基因多态性的个体化给药提供了建议与证据支持。

Effects of genetic polymorphisms on metabolic kinetics,pharmacodynamics and adverse reactions of amitriptyline

Amitriptyline is a tricyclic antidepressant for the treatment of severe depression, post-traumatic stress disorder and other psychiatric diseases, which is widely used in clinical application. However, there are significant individual differences in the response of amitriptyline. Research has shown that genetics polymorphisms of CYP2D6, CYP2C19 and ABCB1 have certain effects on the pharmacokinetics (PK), pharmacodynamics (PD) and adverse reactions (ADR) of amitriptyline. In this paper, we have drawn a preliminary conclusion by comparing the effects of CYP2D6 and CYP2C19 gene polymorphisms on amitriptyline PK, PD and ADR. For CYP2C19 ultrarapid metabolizers or extensive metabolizers, the genetic polymorphism of CYP2D6 has a greater effect on the overall metabolism of amitriptyline. However, for CYP2C19 poor metabolizers, the genetic polymorphisms of CYP2C19 have greater influence. Hopefully, this article can provide genetic-based advice and assistance for the individualized administration of amitriptyline.