PMIO 2017; 4(02): e66-e73
DOI: 10.1055/s-0043-114669
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Multiple Oral Dosing Pharmacokinetics of Standardized Extract of Centella asiatica ECa 233 and Its Inductive Effect on Efflux Transporters in Rats

Tosapol Anukunwithaya1, Mayuree H. Tantisira2, 3, Tsutomu Shimada4, 5, Yoshimichi Sai4, 5, Phisit Khemawoot1, 2
  • 1Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
  • 2Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
  • 3Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand
  • 4Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, Takara-machi, Kanazawa, Japan
  • 5Department of Hospital Pharmacy, University Hospital, Kanazawa University, Takara-machi, Kanazawa, Japan
Further Information

Publication History

received 14 March 2017
revised 15 May 2017

accepted 06 June 2017

Publication Date:
28 August 2017 (online)

Abstract

ECa 233 is a standardized extract of Centella asiatica, characterized as a white powder containing triterpenoid glycosides not less than 80% with a ratio of madecassoside to asiaticoside of 1.5±0.5:1. Although pharmacological and toxicological profiles of ECa 233 have been successively reported, the pharmacokinetic data needed for further therapeutic development are not fully elucidated. This study aimed to investigate the pharmacokinetics of multiple oral dosing of ECa 233 at 100 mg/kg/day for 7 days in rats. Plasma, tissues, urine, and feces were collected from 0 to 24 h after dosing on days 1 and 7. The concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid were simultaneously analyzed by liquid chromatography-tandem mass spectrometry. No significant change was observed in physical and blood biochemical parameters of the animals treated with ECa 233 for 7 days. The maximum plasma concentration and area under the curve at day 7 of madecassoside and asiaticoside decreased by 70–80% from day 1. However, both triterpenoid glycosides were extensively distributed and accumulated, resulting in significantly higher concentrations at pharmacologically relevant organs. Madecasssic acid and asiatic acid are major metabolites mainly found in and excreted via feces. Moreover, multiple dosing of ECa 233 increased mRNA expression of Abcb1a and Abcc2 in the small intestine by approximately 2- to 3-fold. This is the first study to identify an inductive effect of a standardized extract of C. asiatica after multiple oral dosing in rats. Potential drug-herb interactions when ECa 233 is coadministered with Abcb1a and Abcc2 substrates calls for further investigations.

Supporting Information