Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.
Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.
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DOI：
10.1111/cts.12882
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Turgeon J
中科院分区：
文献类型：
--
作者：
Michaud V;Dow P;Al Rihani SB;Deodhar M;Arwood M;Cicali B;Turgeon J
使用重组药物治疗严重急性呼吸系统综合征-冠状病毒2 (SARS - CoV - 2) -相关的2019年传染性冠状病毒病（COVID - 19）的风险-收益比很复杂，因为益处尚待确定，尚未得到证实。我们对5种药物和1种组合（阿奇霉素、氯喹、法匹拉韦、羟氯喹、瑞德西韦和洛匹那韦/利托那韦）用于治疗COVID - 19的药理学特性进行了全面的文献检索。我们进行了与COVID - 19再用途药物相关的药物诱导的长QT综合征（LQTS）风险评估，并与23种已知的反甾原性和10种低反甾原性风险化合物进行了比较。使用药代动力学和药理学数据进行计算机计算，包括阻断由人乙醚- a - go - go基因（hERG）编码的延迟整流心脏钾电流（IKr）快速组分的亲和力，延长心脏复极（QT间期）的倾向和引起点扭转（TdP）。计算并比较了7种不同的LQTS指标。查询美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库，查询与致心律失常事件相关的特定关键词。LQTS风险水平估计值表明，除阿奇霉素外，所有COVID - 19再用途药物的LQTS风险都非常高或中等，尽管已有阿奇霉素类药物的TdP病例报告。用于评估6种再用途药物和23种反致化合物的药物诱导LQTS风险的各种指标之间存在极好的一致性。根据我们的研究结果，当使用一些COVID - 19重新用途的药物时，应进行QT间期监测，因为住院患者或门诊患者使用生物器械时可以进行此类监测。
The risk‐benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2)‐related infectious coronavirus disease 2019 (COVID‐19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID‐19. A risk assessment of drug‐induced long QT syndrome (LQTS) associated with COVID‐19 repurposed drugs was performed and compared with 23 well‐known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether‐a‐go‐go gene (hERG), propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Seven different LQTS indices were calculated and compared. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Estimators of LQTS risk levels indicated a very high or moderate risk for all COVID‐19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug‐induced LQTS for the 6 repurposed medications and 23 torsadogenic compounds. Based on our results, monitoring of the QT interval shall be performed when some COVID‐19 repurposed drugs are used, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients.
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作者：
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