Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats

Authors Gai, Yun-Yun; Liu, Wan-Hui; Sha, Chun-Jie; Wang, Ying-Lin; Sun, Yan-Tong; Li, Xiao-Jiao; Fawcett, J. Paul; Gu, Jing-Kai

Journal JOURNAL OF ETHNOPHARMACOLOGY , ,:

Abstract Ethnopharmacological relevance: 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.Materials and 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 50 mg/kg) and single intravenous (i.v.) doses (5 mg/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 Din 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 21.56-45.09 pmol/mL: T-max 0.46-1.28, 2.00-4.67, 14.67-19.67 and 8.08-14.27 h; 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 4.2 h; clearance 15.7, 0.48, 0.24 and 1.13 mL/h kg.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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Species covered 升麻 Cimicifuga foetida