title: Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats.
abstract: OBJECTIVE
  Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides.
  
  
  METHODS
  Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro.
  
  
  RESULTS
  A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability.
  
  
  CONCLUSIONS
  Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|University of Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jia-zhen
authors.initials: JZ
authors.lastname: Lin
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jun-ling
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Jia
authors.affiliation: Second Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300150, China.
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Fei-fei
authors.initials: FF
authors.lastname: Du
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Feng-qing
authors.initials: FQ
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Mei-juan
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Second Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300150, China.
authors.forename: Yan-fen
authors.initials: YF
authors.lastname: Li
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Na-ting
authors.initials: NT
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Olajide E
authors.initials: OE
authors.lastname: Olaleye
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Now in Laboratory of Phase I Clinical Trials, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Tianjin Chasesun Pharmaceutical Co, Ltd, Tianjin 301700, China.
authors.forename: Chang-hai
authors.initials: CH
authors.lastname: Sun
authors.affiliation: Tianjin Chasesun Pharmaceutical Co, Ltd, Tianjin 301700, China.
authors.forename: Gui-ping
authors.initials: GP
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.|University of Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005260:Female; D005960:Glucosides / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006027:Glycosides / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D039821:Monoterpenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D029596:Paeonia / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D006027:Glycosides; D039821:Monoterpenes; C549376:Xuebijing; C015423:peoniflorin
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