title: Clinical tolerability and pharmacokinetics of Erigerontis hydroxybenzene injection: results of a randomized phase I study in healthy Chinese volunteers.
abstract: Multiple phenolic compounds in the extract of Erigeron breviscapus synergistically contribute to the neurovascular protective effects. We conducted a phase I and pharmacokinetic study with the phenolic compound-enriched product extracted from Erigeron breviscapus, Erigerontis hydroxybenzenes injection (EHI), in healthy Chinese volunteers. A randomized, open-label, single-center, double-arm, dose-escalation study of EHI was conducted. The tolerability of intravenously EHI administrated in single- or multiple-dose (once daily for 7 days) was studied in 40 healthy Chinese volunteers and the pharmacokinetics of EHI was studied in additional 10 volunteers. The tolerated dose of intravenous infusion of EHI in healthy Chinese volunteers was 6 vials (equivalent to 90 mg bioactive phenolic compounds). The main limitations to dose escalation of EHI were transit changes in electrocardiogram and mild, transit increase in alanine aminotransferase. After intravenous administration of EHI, the average systemic clearance of multiple phenolic compounds of scutellarin, 1,3-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid were 131, 29, 262, 112 L/h for male volunteers and 202, 28, 252, 117 L/h for female volunteers. The intervention of intravenous infusion of EHI in healthy Chinese volunteers was generally tolerated. The findings from this study provide data on the tolerability and pharmacokinetics of the extract from Erigeron breviscapus and support further trials.
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: wzju333@hotmail.com.
authors.forename: Wen-Zheng
authors.initials: WZ
authors.lastname: Ju
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, PA, USA. Electronic address: zhaoyang4110@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Shi-Jia
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Dai
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Xiong
authors.affiliation: Department of Clinical Pharmacology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China; Department of Cardiovascular Sciences, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Zhu-Yuan
authors.initials: ZY
authors.lastname: Fang
mesh_terms: D000328:Adult; D047310:Apigenin / Q000097:blood; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000097:blood; D049919:Erigeron / Q000737:chemistry*; D005260:Female; D005965:Glucuronates / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
chemical_list: C487840:1,3-dicaffeoylquinic acid; D005965:Glucuronates; D010936:Plant Extracts; D011801:Quinic Acid; C484876:scutellarin; D002726:Chlorogenic Acid; D047310:Apigenin; C478100:3,4-di-O-caffeoylquinic acid; C100434:3,5-dicaffeoylquinic acid
keywords: Erigeron breviscapus; Pharmacokinetics; Tolerability