Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial

doi:10.1016/j.phymed.2019.152828

	Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial
	Li, Rui 1; Zi, Ming-Jie 1; Gou, Zhong-Ping 4; Zhao, Yun-Li 2; Zhang, Wan-Tong 1; Lu, Fang 1; Cao, Wei-Yi 1; Zhao, Ying-Pan 1; Li, Qing-Na 1; Zhao, Yang 1; Wang, Shu-Ge 1; Gao, Hong-Yang 1; Sun, Ming-Yue 1; Luo, Xiao-Dong2 ; Xiong, Zhi-Li 3; Gao, Rui 1
通讯作者	Luo, Xiao-Dong(xdluo@mail.kib.ac.cn) ; Xiong, Zhi-Li(bearry200@126.com) ; Gao, Rui(Ruigao@126.com)
	2019-08-01
发表期刊	PHYTOMEDICINE
ISSN	0944-7113
卷号	61 页码:13
摘要	Background: Alstonia scholaris (Apocynaceae) was reported to be a rich source of indole alkaloids, which exhibited remarkably bioactivities. The leaf of A. scholaris has been used in 'dai' ethno-medicine for treatment of respiratory diseases, and the defined indole alkaloids from leaf of A. scholaris has been registered as investigational new botanical drug (No. 2011L01436) and was approved for phase I/II clinical trials by China Food and Drug Administration (CFDA). Purpose: The aim of the trial is to evaluate the safety and explore the relationship of dosing frequency and pharmacokinetics after oral administration of capsule of alkaloids from leaf of A. scholaris (CALAS) at different doses. Methods: In this randomized, open-labelled, single-center clinical trial, the safety and pharmacokinetics of CALAS were assessed in eligible healthy Chinese volunteers after oral administration of different doses. Each volunteer (n = 10 per group) received single dose of CALAS from 20 mg, 40 mg, 80 mg to 120 mg orally. The pharmacokinetics of CALAS was investigated in healthy Chinese subjects' plasma by a fully-validated LC-MS/MS method. Safety was assessed biochemically and clinically throughout the study, and drug re-excitation research was conducted to verify the correlation between investigational product and minor adverse events. The trial was registered on August 26, 2015 (http://www.chictr. org.cn/showproj.aspx?proj = 11736), number ChiCTR-IPR-15006976. Results: 40 subjects completed the study, and as a result, vallesamine had the highest concentration in plasma of healthy volunteers, and the AUC exposure level in each compounds in turn is vallesamine > scholaricine > 19-epischolaricine > picrinine. For the safety evaluation of CALAS, two cases of minor adverse events were observed during the trial, but the drug re-excitation research indicated that these two adverse events were related to the individual's physiological variation. Conclusion: Pharmacokinetic characteristics of each ingredient showed different patterns. 19-epischolaricine, vallesamine and picrinine were match to the linear pharmacokinetic characteristics, but scholaricine conformed to the characteristics of nonlinear pharmacokinetics. The CALAS was safe in healthy subjects under the current dose regimen.
关键词	Capsule of alkaloids from leaf of A. scholaris (CALAS) Pharmacokinetics Safety evaluation Drug re-excitation research
DOI	10.1016/j.phymed.2019.152828
收录类别	SCI ; SCI
语种	英语
WOS记录号	WOS:000492729600027
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/70197
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Luo, Xiao-Dong; Xiong, Zhi-Li; Gao, Rui
作者单位	1.Chinese Med Sci, China Acad, Clin Pharmacol Inst, Xiyuan Hosp, Beijing 100091, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 3.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Liaoning, Peoples R China 4.Sichuan Univ, West China Hosp, Inst Drug Clin Trials, Chengdu 610041, Sichuan, Peoples R China
推荐引用方式 GB/T 7714	Li, Rui,Zi, Ming-Jie,Gou, Zhong-Ping,et al. Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial[J]. PHYTOMEDICINE,2019,61:13.
APA	Li, Rui.,Zi, Ming-Jie.,Gou, Zhong-Ping.,Zhao, Yun-Li.,Zhang, Wan-Tong.,...&Gao, Rui.(2019).Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial.PHYTOMEDICINE,61,13.
MLA	Li, Rui,et al."Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial".PHYTOMEDICINE 61(2019):13.

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