国家神经系统疾病临床医学研究中心数据管理与共享系统

Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases

《国家中心数据管理与共享系统操作说明书 —— 研究者部分》

Bioavailability of Edaravone Sublingual Tablet Versus Intravenous Infusion in Healthy Male Volunteers

第一作者：Jiaqing Wang,Xia Chen

通讯作者：Yongjun Wang,Xia Chen

bioavailability edaravone intravenous injection

基本信息

2018-09-18

已发表文章

发表杂志：Clinical Therapeutics

发表类型: Original Contributions

影响因子(IF): 3.393

PMID: 30241688 Pubmed原文链接 全文下载

主要研究背景及目的

Edaravoneisa free-radicalscavenger.Edaravone 30 mg IV has been approved for use in the treatment of acute ischemic stroke in Japan and China, and for amyotrophic lateral sclerosis in Japan and the United States. Considering the inconvenience of IV infusion in clinical practice, an oral tablet formulation of edaravone was developed but failed in 2011 due to poor bioavailability. More recently, a sublingual (SL) tablet formulation of edaravone 30 mg was developed by a Good Manufacturing Practicescompliant manufacturer in China. This study explored the bioavailability of the SL tablet of edaravone and aimed to provide evidence to support decision making in future clinical development

方法

This 2-way crossover study was conducted in 10 healthy male volunteers. Eligible subjects were randomized,in a 1:1ratio,to1of 2 dosing sequences:(1)SL edaravone30 mg,followed by edaravone 30 mg IV infusion given over 30 minutes; or (2) edaravone 30 mg IV infusion given over 30 minutes, followed by SL edaravone 30 mg. The washout period between the 2 dosing periods was at least 24 hours. Serial blood samples were collected in each dosing period.The bioavailability of the SL tablet was assessed using bioavailability analysis.Tolerability was evaluated throughout the study

结论

The bioavailability of the SL tablet of edaravone was 91.94%. Compared with IV administration, Cmax with SL administration was»17% lower and Tmax was statistically significantly longer. The exposure differences can be addressed by modifying the strength of the SL tablet, and then conducting a second study to demonstrate the pharmacokinetic bioavailability of the sublingually administered new strength versus IV infusion of edaravone.

主要结果

The plasma concentrationtime profile of the SL tablet was similar to that with the IV infusion. A mean (SD) Cmax of 2030.2 (517.2) ng/mL was reached within a median Tmax of 0.875 hour, which was statistically significantly longer than the median Tmax with IV administration (0.5 hour). The Cmax with SL administration corresponded to 83.92% (90% CI, 73.22%96.18%) of the Cmax with the start of IV infusion (2354.0 [336.6] ng/mL). The mean AUC0t with SL dosing was 5420.07 (1429.75) h ¢ ng/mL, which corresponded to 91.94% (90% CI, 86.81%97.39%) of the AUC0t with IV administration (5824.42 [1338.48] h ¢ ng/mL). Two cases of adverse events were reported during the study; both were considered by the investigator to have been possibly not related to the study treatment.