Certara, Princeton, NJ, USA.
Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Br J Clin Pharmacol. 2021 Sep;87(9):3388-3397. doi: 10.1111/bcp.14760. Epub 2021 Feb 23.
During a pandemic caused by a novel pathogen (NP), drug repurposing offers the potential of a rapid treatment response via a repurposed drug (RD) while more targeted treatments are developed. Five steps of model-informed drug repurposing (MIDR) are discussed: (i) utilize RD product label and in vitro NP data to determine initial proof of potential, (ii) optimize potential posology using clinical pharmacokinetics (PK) considering both efficacy and safety, (iii) link events in the viral life cycle to RD PK, (iv) link RD PK to clinical and virologic outcomes, and optimize clinical trial design, and (v) assess RD treatment effects from trials using model-based meta-analysis. Activities which fall under these five steps are categorized into three stages: what can be accomplished prior to an NP emergence (preparatory stage), during the NP pandemic (responsive stage) and once the crisis has subsided (retrospective stage). MIDR allows for extraction of a greater amount of information from emerging data and integration of disparate data into actionable insight.
在由新型病原体（NP）引起的大流行期间，药物重新定位通过重新定位药物（RD）提供了快速治疗反应的潜力，同时开发更有针对性的治疗方法。讨论了模型驱动的药物重新定位（MIDR）的五个步骤：（i）利用 RD 产品标签和体外 NP 数据来确定初始潜在性的初步证据，（ii）考虑疗效和安全性，使用临床药代动力学（PK）优化潜在的治疗方案，（iii）将病毒生命周期中的事件与 RD PK 联系起来，（iv）将 RD PK 与临床和病毒学结果联系起来，并优化临床试验设计，以及（v）使用基于模型的荟萃分析评估来自试验的 RD 治疗效果。属于这五个步骤的活动分为三个阶段：在 NP 出现之前（准备阶段）可以完成的活动，NP 大流行期间（响应阶段）和危机消退后（回顾阶段）。MIDR 允许从新兴数据中提取更多信息，并将不同的数据整合为可操作的见解。
