title: Pharmacokinetics and tolerance of toal astragalosides after intravenous infusion of astragalosides injection in healthy Chinese volunteers.
abstract: Total astragalosides (TA) are the principal active constituents isolated from Radix Astragali, which has been extensively used in the traditional Chinese medicine for hundreds of years. However, few detailed pharmacokinetic studies about TA or its main component in human have been done to date. The aim of this study was to investigate the pharmacokinetic (PK) characteristics of astragaloside IV (AGS-IV), the primary ingredient of TA, and tolerance of TA after single- and multi-intravenous infusion of astragalosides injection (AI) in healthy Chinese volunteers. A LC-MS/MS assay was developed for AGS-IV determination in human plasma and urine, and the PK parameters were estimated using non-compartmental methods. The mean maximum plasma concentration (Cmax) values of AGS-IV were 2.12, 3.59, 3.71 and 5.17 μg ml(-1) after single doses of 200, 300, 400 and 500 ml of AI, respectively. The corresponding mean values of area under the plasma concentration (AUC(0-∞)) were 4.38, 9.75, 13.59 and 18.22 μg h ml(-1), respectively, and the mean values of elimination half-life (t1/2) were 2.14, 2.59, 2.62 and 2.69 h, respectively. In the repeated dose study, no significant difference was observed between the PK parameters, peak time (Tmax), t1/2 and AUC, of day 1 and day 7. Cumulative urinary excretion of AGS-IV was 3.91% within 24 h after administration of 500 ml AI. AI was safe and well tolerated, and the adverse events, such as raised total bilirubin and rash, were mild and resolved spontaneously. In summary, the pharmacokinetic properties of AGS-IV are based on linear pharmacokinetics over the doses ranging from 200 to 500 ml of AI. No accumulation of AGS-IV was observed after repeated administration of AI once daily. AI was safe and well tolerated in this study, although cases of transient adverse events were observed.
authors.affiliation: Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing 210029, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Xu
authors.forename: Jungang
authors.initials: J
authors.lastname: Yin
authors.forename: Liyan
authors.initials: L
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Chong
authors.initials: C
authors.lastname: Zou
authors.forename: Jiandong
authors.initials: J
authors.lastname: Zou
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Ju
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000328:Adult; D029971:Angelica sinensis / Q000737:chemistry*; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012503:Saponins / Q000009:adverse effects / Q000493:pharmacokinetics*; D013997:Time Factors; D014315:Triterpenes / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A
keywords: Astragaloside IV (AGS-IV); Human; Pharmacokinetics; Radix Astragali; Tolerance; Total astragalosides