Drugs in COVID-19 Clinical Trials: Predicting Transporter-Mediated Drug-Drug Interactions Using In Vitro Assays and Real-World Data.
Drugs in COVID-19 Clinical Trials: Predicting Transporter-Mediated Drug-Drug Interactions Using In Vitro Assays and Real-World Data.
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DOI：
10.1002/cpt.2236
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发表时间：
2021-07
影响因子：
6.7
通讯作者：
Giacomini KM
中科院分区：
文献类型：
--
作者：
Yee SW;Vora B;Oskotsky T;Zou L;Jakobsen S;Enogieru OJ;Koleske ML;Kosti I;Rödin M;Sirota M;Giacomini KM
目前有多种治疗 2019 冠状病毒病 (COVID-19) 的药物正在进行加速临床研究；然而，这些药物的既定安全性和有效性数据有限。本研究的目的是预测 COVID-19 临床试验中 25 种小分子药物引起临床相关药物相互作用 (DDI) 的潜力，这种相互作用可能导致使用伴随药物时潜在的药物不良反应 (ADR)。我们重点关注 11 家运输公司，它们是 DDI 的目标。对表达转运蛋白的膜囊泡或 HEK293 细胞的体外效力研究与 DDI 风险评估方法相结合，显示 25 种药物中有 20 种符合监管机构的标准，引发了 DDI 临床试验的考虑。对电子健康记录（包括代表近 120,000 名 COVID-19 患者的数据库）的真实世界数据的分析与导致转运蛋白介导的 DDI 的几种药物（例如西地那非、氯喹和羟氯喹）一致。这项研究表明，COVID-19 患者通常年龄较大且正在服用各种合并药物，应仔细监测 ADR。未来的临床研究需要确定预测在临床相关浓度下抑制转运蛋白的药物是否真的会导致 DDI。
Numerous drugs are currently under accelerated clinical investigation for the treatment of coronavirus disease 2019 (COVID‐19); however, well‐established safety and efficacy data for these drugs are limited. The goal of this study was to predict the potential of 25 small molecule drugs in clinical trials for COVID‐19 to cause clinically relevant drug‐drug interactions (DDIs), which could lead to potential adverse drug reactions (ADRs) with the use of concomitant medications. We focused on 11 transporters, which are targets for DDIs. In vitro potency studies in membrane vesicles or HEK293 cells expressing the transporters coupled with DDI risk assessment methods revealed that 20 of the 25 drugs met the criteria from regulatory authorities to trigger consideration of a DDI clinical trial. Analyses of real‐world data from electronic health records, including a database representing nearly 120,000 patients with COVID‐19, were consistent with several of the drugs causing transporter‐mediated DDIs (e.g., sildenafil, chloroquine, and hydroxychloroquine). This study suggests that patients with COVID‐19, who are often older and on various concomitant medications, should be carefully monitored for ADRs. Future clinical studies are needed to determine whether the drugs that are predicted to inhibit transporters at clinically relevant concentrations, actually result in DDIs.
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影响因子：
4.5
作者：
Morrissey KM;Stocker SL;Chen EC;Castro RA;Brett CM;Giacomini KM
通讯作者：
Giacomini KM
影响因子：
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通讯作者：
Giacomini KM
影响因子：
4.2
作者：
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通讯作者：
Klarin, Inga