Comparative pharmacokinetic study of asiaticoside and madecassoside as the pure compounds and mixture in the standardized extract of centella asiatica, ECa 233 in rats

Abstract

ECa 233, the standardized extract of Centella asiatica, contains not less than 80% triterpenoid glycosides, in a madecassoside:asiaticoside ratio of 1.5 (± 0.5): 1. In this study, we performed a pharmacokinetic comparison of madecassoside and asiaticoside following intravenous and oral administration of ECa 233, or an equivalent dose of the individual compounds, in rats. Blood, tissues, urine and feces were collected after dosing for the determination of drug and metabolite levels using liquid chromatography-tandem mass spectrometry. The results revealed that plasma levels of madecassoside, and to a lesser extent asiaticoside, were higher after administration of ECa 233 than the corresponding values for the pure compounds. The elimination half-life of madecassoside and asiaticoside were significantly prolonged after administration of ECa 233 (p < 0.05). The mean resident time of asiaticoside appeared to be prolonged following the oral administration of ECa 233 compared with following administration of the pure asiaticoside (12.79 vs 7.20 h). Interestingly, there was a bidirectional interconversion between asiaticoside and madecassoside consistent with the increased exposure of madecassoside and asiaticoside in ECa 233. In tissue distribution studies, asiaticoside and madecassoside appeared to be widely distributed in several organs. Both madecassoside and asiaticoside were metabolized extensively; following intravenous administration of either compound, approximately 80-90% of the dose was recovered as madecasssic acid and asiatic acid in the feces.