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Planta Med 2017; 83(08): 710-717
DOI: 10.1055/s-0042-122344
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics of a Standardized Extract of Centella asiatica ECa 233 in Rats

Tosapol Anukunwithaya
1   Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
,
Mayuree H. Tantisira
2   Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand
3   Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
,
Boonyong Tantisira
1   Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
,
Phisit Khemawoot
1   Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
3   Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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Publikationsverlauf

received 11. April 2016
revised 09. November 2016

accepted 22. November 2016

Publikationsdatum:
19. Dezember 2016 (online)

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Abstract

ECa 233, a standardized extract of Centella asiatica, has been found to exhibit various positive neurological effects and to have a good safety profile. The present study aimed to explore the disposition kinetics of ECa 233, containing madecassoside (53.1 %) and asiaticoside (32.3 %), in rats. The extract was intravenously or orally administered at doses from 50 to 200 mg/kg. Plasma, tissues, urine, and feces were collected at time points from 0 to 48 h after dosing. The levels of madecassoside and asiaticoside, as well as their postulated triterpenic metabolites, madecassic acid and asiatic acid, in biological samples, were simultaneously measured by liquid chromatography-tandem mass spectrometry. The results showed that all animals had a good tolerability for ECa 233, whereas madecassic and asiatic acids were found in negligible amounts after pharmacokinetic assessment. Madecassoside and asiaticoside demonstrated rather similar absorption and tissue distribution profiles. They were rapidly absorbed, reaching maximum levels within 5–15 min after oral administration, but they had poor oral bioavailability, less than 1 %. Both triterpenoids were extensively distributed in the brain, stomach, and skin within 1 h and remained there for at least 4 h after dosing. Madecassoside and asiaticoside in ECa 233 were mainly excreted as an unchanged form after being injected, and exclusively as triterpenic acid metabolites in feces after oral administration. The pharmacokinetic results obtained could provide some guidance for an appropriate dosing regimen of ECa 233 in future studies. This study also provided the first evidence demonstrating the presence of madecassoside and asiaticoside in their target tissues.

Key words

Centella asiatica - Apiaceae - ECa 233 - madecassoside - asiaticoside - pharmacokinetics

Supporting Information

Mass spectrometry parameters of standard chemicals used for measurements in biological samples, the partial method validation data of the compounds, and LC-MS/MS chromatograms for ECa 233 are available as Supporting Information.

 

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