Investigation on pharmacochemistry and pharmacokinetics of atractylenolides from Atractylodes in vivo based on UPLC-MS combined with everted gut sac model in vitro

Abstract

The article aimed to study intestinal absorption and pharmacokinetic characterization of three atractylenolides from low polar component of Atractylodes (LPA). LC-MS method was used to find absorbed components combined with pharmacochemistry and to determine plasma concentration combined with DAS 3.0 to calculate the PK parameters. Moreover, the everted gut sac model was used to investigate rat small intestinal absorption and transport characterization of atractylenolide I, II, III. In total, eight components were identified from the absorbed components, including two lactones (6, 7), three volatile oil (2, 3, 8), acids (1), prenylated dihydrobenzofuran derivative (4) and luteolin (5), respectively. The three atractylenolides are rapidly absorbed with Tmax as 1 h and more compatible with the two-compartment model in rats, and good linearity between Cmax and concentration. The cumulative absorption per unit area Q (ug·cm−2) of three atractylenolides were no significant difference and all linearly absorbed with different time, concentration in different intestinal segments, which indicated its absorption process was passive transport. In addition, the atractylenolides III showed most high absorption rate in all intestinal segments, and the absorption site of atractylenolides II was mainly duodenum segments. LC-MS is a systematically applicable approach for rapid screening, identification and quanlitation of absorbed components derived from atractylodes in vivo. Three atractylenolides showed similar PK characterization and passive transport through all intestinal segments. It looks more safe with less drug interaction.