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A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects

文献类型：期刊论文

作者Yang, Xin-Mei6,7; Yang, Yang5; Yao, Bu-Fan4; Ye, Pan-Pan6,7; Xu, Yan3; Peng, Shao-Ping5; Yang, Yu-Mei5; Shu, Pan5; Li, Pei-Jin5; Li, Shan5
刊名EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
出版日期2023-12-01
卷号191页码:9
关键词COVID-19 Simnotrelvir Safety Pharmacokinetics Healthy subjects
ISSN号0928-0987
DOI10.1016/j.ejps.2023.106598
通讯作者Zhao, Wei(zhao4wei2@hotmail.com)
英文摘要Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.
资助项目National Key Research and Development Program of China[2022YFC0868600] ; Jiangsu Simcere Pharmaceutical Co., Ltd.
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001096459800001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/307724]  
专题中国科学院上海药物研究所
通讯作者Zhao, Wei
作者单位1.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, State Key Lab Virol, Wuhan, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Simcere Amer, Cambridge, MA USA
4.Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Clin Pharm,Key Lab Chem Biol,Minist Educ, Jinan, Peoples R China
5.Jiangsu Simcere Pharmaceut Co Ltd, Nanjing, Peoples R China
6.Shandong Prov Qianfoshan Hosp, Shandong Engn & Technol Res Ctr Pediat Drug Dev, Shandong Med & Hlth Key Lab Clin Pharm, Jinan, Peoples R China
7.Shandong First Med Univ, Affiliated Hosp 1, Dept Clin Pharm, Jinan, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Xin-Mei,Yang, Yang,Yao, Bu-Fan,et al. A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2023,191:9.
APA Yang, Xin-Mei.,Yang, Yang.,Yao, Bu-Fan.,Ye, Pan-Pan.,Xu, Yan.,...&Zhao, Wei.(2023).A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,191,9.
MLA Yang, Xin-Mei,et al."A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 191(2023):9.

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来源：上海药物研究所

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