title: Pharmacokinetics of escin Ia in rats after intravenous administration.
abstract: BACKGROUND
  Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years. The goal of this study is to investigate the pharmacokinetic behavior of escin Ia in rats after low, medium and high-dose intravenous administration.
  
  
  METHODS
  Wistar rats were divided into 3 groups (n=6 per group) and escin Ia was administered via the caudal vein at doses of 0.5, 1.0 and 2.0 mg/kg, respectively. Subsequently, the concentrations of escin Ia and its metabolite isoescin Ia, a positional isomer of escin Ia, in rats׳ plasma were measured by an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method at various time points following the administration of the drug. Main pharmacokinetic parameters were calculated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany).
  
  
  RESULTS
  After intravenous administration, the Cmax and AUC of escin Ia increased in a dose-proportional manner at the dose of 0.5 mg/kg and 1.0 mg/kg, while increased in a more than dose-proportional manner at the doses of 1.0 mg/kg and 2.0 mg/kg. The t₁/₂ was significantly longer with increased intravenous doses, while other parameters such as CL and Vd also exhibit disagreement among three doses. Taken together, our data showed dose-dependent pharmacokinetic profile of escin Ia in rats after intravenous administration at the doses of 0.5-2.0 mg/kg. After intravenous administration, escin Ia was rapidly and extensively converted to isoescin Ia.
  
  
  CONCLUSIONS
  The results suggested dose-dependent pharmacokinetics of escin Ia at the doses of 0.5-2.0 mg/kg after intravenous administration. Escin Ia is isomerized to isoescin Ia rapidly and extensively regardless of the doses.
authors.affiliation: Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, China; Research Center for Drug Metabolism, Jilin University, 2699 Qianjin Road, Changchun 130012, China.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Research Center for Drug Metabolism, Jilin University, 2699 Qianjin Road, Changchun 130012, China.
authors.forename: Xiang-Yong
authors.initials: XY
authors.lastname: Cui
authors.affiliation: No.4 west china hospital, Sichuan University, Chengdu, Sichua 610041, China.
authors.forename: Lian-tian
authors.initials: LT
authors.lastname: Tian
authors.affiliation: Research Center for Drug Metabolism, Jilin University, 2699 Qianjin Road, Changchun 130012, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Research Center for Drug Metabolism, Jilin University, 2699 Qianjin Road, Changchun 130012, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Research Center for Drug Metabolism, Jilin University, 2699 Qianjin Road, Changchun 130012, China. Electronic address: gujk@mail.jlu.edu.cn.
authors.forename: Jing-Kai
authors.initials: JK
authors.lastname: Gu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004928:Escin / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D004928:Escin; C115101:escin Ia
keywords: Escin Ia; Isoescin Ia; Isomerization; LC–MS/MS; Pharmacokinetics; Rats