Pharmacokinetics and safety evaluation in healthy Chinese volunteers of alkaloids from leaf of Alstonia scholaris: A multiple doses phase I clinical trial
Li, Rui1; Zi, Ming-Jie1; Gou, Zhong-Ping4; Zhao, Yun-Li2; Zhang, Wan-Tong1; Lu, Fang1; Cao, Wei-Yi1; Zhao, Ying-Pan1; Li, Qing-Na1; Zhao, Yang1; Wang, Shu-Ge1; Gao, Hong-Yang1; Sun, Ming-Yue1; Luo, Xiao-Dong2; Xiong, Zhi-Li3; Gao, Rui1
Corresponding AuthorLuo, Xiao-Dong(xdluo@mail.kib.ac.cn) ; Xiong, Zhi-Li(bearry200@126.com) ; Gao, Rui(Ruigao@126.com)
2019-08-01
Source PublicationPHYTOMEDICINE
ISSN0944-7113
Volume61Pages:13
AbstractBackground: 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.
KeywordCapsule of alkaloids from leaf of A. scholaris (CALAS) Pharmacokinetics Safety evaluation Drug re-excitation research
DOI10.1016/j.phymed.2019.152828
Indexed BySCI ; SCI
Language英语
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000492729600027
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/70197
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorLuo, Xiao-Dong; Xiong, Zhi-Li; Gao, Rui
Affiliation1.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
Recommended Citation
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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