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Development and validation of a UHPLC-MS/MS method for quantification of the prodrug remdesivir and its metabolite GS-441524: a tool for clinical pharmacokinetics of SARS-CoV-2/COVID-19 and Ebola virus disease
Journal of Antimicrobial Chemotherapy ( IF 3.9 ) Pub Date : 2020-05-03 , DOI: 10.1093/jac/dkaa152
Valeria Avataneo 1 , Amedeo de Nicolò 1 , Jessica Cusato 1 , Miriam Antonucci 1 , Alessandra Manca 1 , Alice Palermiti 1 , Catriona Waitt 2, 3 , Stephen Walimbwa 3 , Mohammed Lamorde 3 , Giovanni di Perri 1, 4 , Antonio D’Avolio 1, 4
Affiliation  

Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification.

中文翻译:

开发和验证用于定量前药瑞德昔韦及其代谢产物GS-441524的UHPLC-MS / MS方法:SARS-CoV-2 / COVID-19和埃博拉病毒病的临床药代动力学工具

雷姆昔韦在治疗SARS-CoV-2引起的COVID-19中的潜在应用受到了广泛的关注。Remdesivir已通过埃博拉病毒病治疗测试,并具有抗SARS和MERS冠状病毒的活性。remdesivir核心含有GS-441524,它仅干扰RNA依赖性RNA聚合酶。在非人灵长类动物中,静脉内给药后,瑞德昔韦迅速分布到PBMC中,并在2小时内转化为活性核苷三磷酸形式,而GS-441524在血浆中的检测时间长达24小时。尽管如此,瑞姆昔韦在人体内的药代动力学和药效学仍未得到探索,这凸显了对瑞姆昔韦和GS-441524定量分析的精确分析方法的需求。
更新日期:2020-06-19
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