Pharmacokinetic Change of Glycyrrhetinic Acid from the Roots and Rhizomes of Glycyrrhiza uralensis by Coadministration with the Rhizomes of Atractylodes japonica, A. macrocephala, or A. chinensis in an Animal Model

Abstract

Atractylodes rhizomes (Atractylodes japonica Koidz. ex Kitam., A. macrocephala Koidz., and A. chinensis), Asteraceae, are widely used to treat digestive disorders and these rhizomes are commonly paired with the roots and rhizomes of Glycyrrhiza uralensis Fisch., Fabaceae, in herbal formulae, which may lead to mutual interaction in vivo. To assess the influence of three species of Atractylodes rhizomes on the pharmacokinetic features of G. uralensis, the levels of glycyrrhetinic acid in rat plasma samples were quantified using ultra-performance liquid chromatography/ion-trap mass spectrometry after intragastric coadministration. The results demonstrated that simultaneous administration of the extracts of the three Atractylodes rhizomes reduced the mean residence time and last measured concentration of glycyrrhetinic acid in plasma samples. Among the Atractylodes rhizomes, the combination of A. japonica shortened the elimination half-life and time to the maximum concentration of glycyrrhetinic acid. In conclusion, Atractylodes rhizomes, especially A. japonica, might alter the pharmacokinetic characteristics (mostly the duration in vivo) of glycyrrhetinic acid from G. uralensis when these herbs are coadministered. This study provides an understanding for species-specific influences on pharmacokinetic features in herbal combinations.