Influence of CYP2D6 genetic variation on adverse events with propafenone in the pediatric and young adult population.
Influence of CYP2D6 genetic variation on adverse events with propafenone in the pediatric and young adult population.
复制标题
CYP2D6基因变异对普罗帕酮在儿童和年轻成人人群中不良事件的影响
DOI：
10.1111/cts.13296
复制
发表时间：
2022-07
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
普罗帕酮是一种抗心律失常药物，主要通过细胞色素 P450 2D6 (CYP2D6) 代谢。在成人中，普罗帕酮不良事件 (AE) 与 CYP2D6 代谢状态较差有关；然而，缺乏儿科数据。测试了受试者的 10 个 CYP2D6 等位基因变异和拷贝数状态，以及分配给每个基因型的活性评分。包括 76 人（中位年龄 0.3 [范围 0-26] 岁）。普罗帕酮 AE 发生率为 29 例 (38%)； 14 名 (18%) 因 AE 需要停药。最常见的 AE 是 QRS (n = 10) 和 QTc (n = 6) 延长。患有 AE 的患者在开始使用普罗帕酮时年龄较大（1.58 [0.13–9.92] vs. 0.20 [0.08–2.01] 岁；p = 0.042）。 CYP2D6 活动评分与 AE 的存在无关（比值比 [OR] 0.48 [0.22–1.03]；p = 0.055），但与 AE 总数（β 1 = -0.31 [-0.60, -0.03]；p = 0.029）、系统性 AE（OR 0.33）相关。 [0.13–0.88]；p = 0.022），以及因全身性 AE 停药（OR 0.28 [0.09–0.83]；p = 0.017）。了解 CYP2D6 活动评分和患者年龄可能有助于确定个体在服用普罗帕酮后发生 AE 的风险。
Propafenone is an antiarrhythmic drug metabolized primarily by cytochrome P450 2D6 (CYP2D6). In adults, propafenone adverse events (AEs) are associated with CYP2D6 poor metabolizer status; however, pediatric data are lacking. Subjects were tested for 10 CYP2D6 allelic variants and copy number status, and activity scores assigned to each genotype. Seventy‐six individuals (median 0.3 [range 0–26] years old) were included. Propafenone AEs occurred in 29 (38%); 14 (18%) required drug discontinuation due to AE. The most common AEs were QRS (n = 10) and QTc (n = 6) prolongation. Those with AEs were older at the time of propafenone initiation (1.58 [0.13–9.92] vs. 0.20 [0.08–2.01] years old; p = 0.042). CYP2D6 activity scores were not associated with presence of an AE (odds ratio [OR] 0.48 [0.22–1.03]; p = 0.055) but with the total number of AE (β 1 = −0.31 [−0.60, −0.03]; p = 0.029), systemic AEs (OR 0.33 [0.13–0.88]; p = 0.022), and drug discontinuation for systemic AEs (OR 0.28 [0.09–0.83]; p = 0.017). Awareness of CYP2D6 activity score and patient age may aid in determining an individual's risk for an AE with propafenone administration.
登录
查看更多内容
影响因子：
6.7
作者：
McGregor, T. L.;Van Driest, S. L.;Brothers, K. B.;Bowton, E. A.;Muglia, L. J.;Roden, D. M.
通讯作者：
Roden, D. M.
影响因子：
2.1
作者：
Doki, Kosuke;Shirayama, Yuki;Homma, Masato
通讯作者：
Homma, Masato
影响因子：
6.7
作者：
Moerike, K.;Kivistoe, K. T.;Schwab, M.
通讯作者：
Schwab, M.
影响因子：
158.5
作者：
LEE, JT;KROEMER, HK;WOOSLEY, RL
通讯作者：
WOOSLEY, RL
影响因子：
2.8
作者：
REIMER, A;PAUL, T;KALLFELZ, HC
通讯作者：
KALLFELZ, HC