CYP2C19型
依西酞普兰
CYP2D6型
西酞普兰
药物遗传学
药理学
舍曲林
医学
帕罗西汀
基因分型
药物基因组学
内科学
基因型
生物
遗传学
基因
抗抑郁药
细胞色素P450
新陈代谢
海马体
作者
Jolijn Brouwer,Marga Nijenhuis,Bianca Soree,Henk‐Jan Guchelaar,Jesse J. Swen,Ron H.N. van Schaik,Jan van der Weide,Gerard A. Rongen,Anne‐Marie Buunk,Nienke J de Boer-Veger,Elisa J. F. Houwink,Roos van Westrhenen,Bob Wilffert,Vera H.M. Deneer,Hans Mulder
标识
DOI:10.1038/s41431-021-01004-7
摘要
The Dutch Pharmacogenetics Working Group (DPWG) guideline presented here, presents the gene-drug interaction between the genes CYP2C19 and CYP2D6 and antidepressants of the selective serotonin reuptake inhibitor type (SSRIs). Both genes’ genotypes are translated into predicted normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), or ultra-rapid metabolizer (UM). Evidence-based dose recommendations were obtained, based on a structured analysis of published literature. In CYP2C19 PM patients, escitalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 75% of the normal maximum dose. Escitalopram should be avoided in UM patients. In CYP2C19 PM patients, citalopram dose should not exceed 50% of the normal maximum dose. In CYP2C19 IM patients, this is 70% (65–75%) of the normal maximum dose. In contrast to escitalopram, no action is needed for CYP2C19 UM patients. In CYP2C19 PM patients, sertraline dose should not exceed 37.5% of the normal maximum dose. No action is needed for CYP2C19 IM and UM patients. In CYP2D6 UM patients, paroxetine should be avoided. No action is needed for CYP2D6 PM and IM patients. In addition, no action is needed for the other gene-drug combinations. Clinical effects (increase in adverse events or decrease in efficacy) were lacking for these other gene-drug combinations. DPWG classifies CYP2C19 genotyping before the start of escitalopram, citalopram, and sertraline, and CYP2D6 genotyping before the start of paroxetine as “potentially beneficial” for toxicity/effectivity predictions. This indicates that genotyping prior to treatment can be considered on an individual patient basis.
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