Pharmacokinetics and bioavailability of cimicifugosides after oral administration of Cimicifuga foetida L. extract to rats.
J Ethnopharmacol
; 143(1): 249-55, 2012 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-22771280
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 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 20.71.42.91. 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
/
Cimicifuga
/
Lanosterol
Limite:
Animals
Idioma:
En
Revista:
J Ethnopharmacol
Ano de publicação:
2012
Tipo de documento:
Article