title: Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats.
abstract: BACKGROUND
  Cimicifuga foetida L., a traditional Chinese medicine, has been used as an anti-inflammatory, antipyretic and analgesic remedy. The primary active constituents are believed to be present in the triterpene glycoside fraction.
  
  
  METHODS
  To develop an LC-MS/MS assay for four major cimicifugosides [cimicifugoside H-1 (Cim A), 23-epi-26-deoxyactein (Cim B), cimigenolxyloside (Cim C) and 25-O-acetylcimigenoside (Cim D)] obtained from C. foetida L. and apply it to investigate their pharmacokinetic (PK) properties and bioavailabilities through oral administration of C. foetida L. extract (12.5, 25 and 50mg/kg) and single intravenous (i.v.) doses (5mg/kg) of the individual cimicifugosides in rat. PK parameters were estimated by non-compartmental analysis.
  
  
  RESULTS
  All calibration curves showed excellent linear regressions (all r>0.995) within the range of tested concentrations. The intra- and inter-day variations were <15% in terms of RSD. The molar ratio of Cims A, B, C, and D in the extract was 20.7:1.4:2.9:1. PK parameters for Cims A, B, C, and D following oral administration of the extract were respectively: C(max) 4.05-17.69, 90.93-395.7, 407.1-1180 and 21.56-45.09pmol/mL; T(max) 0.46-1.28, 2.00-4.67, 14.67-19.67 and 8.08-14.27h; absolute oral bioavailability (F) 1.86-6.97%, 26.8-48.5%, 238-319% and 32.9-48%. PK parameters after i.v. administration of individual cimicifugosides were respectively: elimination half-life 1.1, 2.5, 5.7 and 4.2h; clearance 15.7, 0.48, 0.24 and 1.13mL/hkg.
  
  
  CONCLUSIONS
  Systemic exposure to Cims B, C and D following oral administration of the extract was significantly greater than to Cim A despite the predominance of Cim A in the extract. Significantly different clearance and interconversion from Cim A to Cim C probably accounts for the different exposure to the four cimicifugosides.
authors: Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130012, PR China.
authors: Yun-Yun
authors: YY
authors: Gai
authors: Wan-Hui
authors: WH
authors: Liu
authors: Chun-Jie
authors: CJ
authors: Sha
authors: Ying-Lin
authors: YL
authors: Wang
authors: Yan-Tong
authors: YT
authors: Sun
authors: Xiao-Jiao
authors: XJ
authors: Li
authors: J
authors: J
authors: Paul Fawcett
authors: Jing-Kai
authors: JK
authors: Gu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D031885:Cimicifuga / Q000737:chemistry*; D007810:Lanosterol / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D016014:Linear Models; D010936:Plant Extracts / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; D007810:Lanosterol