Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema.

AIM OF THE STUDY:

To establish a sensitive LC-MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported.

MATERIALS AND METHODS:

Wister rats were administrated an intravenous (i.v.) dose (1.7 mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC-MS/MS method. Main pharmacokinetic parameters including t(1/2), MRT, CL, V(d), AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance.

RESULTS:

After administration of sodium escinate, the t(1/2) and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia.

CONCLUSION:

Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other.

• Authors: Xiu-Jun Wu, Meng-Liang Zhang, Xiang-Yong Cui, Feng Gao, Qun He, Xiao-Jiao Li, Ji-Wen Zhang, J Paul Fawcett, Jing-Kai Gu
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 139 Issue 1 Pg. 201-6 (Jan 06 2012) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 22094055 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Plant Extracts
• Escin
• escin Ia

Topics

• Administration, Oral
• Aesculus (chemistry)
• Animals
• Area Under Curve
• Biological Availability
• Chromatography, Liquid
• Escin (analogs & derivatives, blood, isolation & purification, pharmacokinetics)
• Female
• Injections, Intravenous
• Male
• Plant Extracts (blood, pharmacokinetics)
• Rats
• Rats, Wistar
• Seeds (chemistry)
• Tandem Mass Spectrometry