Abstract
The objective of this study was to characterize pharmacokinetics (PKs) of kaurenoic acid (KAU) after administration of the clinical usual dose of Araliae Continentalis Radix extract powder to Korean subjects for the first time and evaluate the mechanism of its absorption in vitro. A simple, sensitive, and selective analytical method was developed for the detection of KAU in human plasma. Concentrations of KAU were quantified by ultra-performance liquid chromatography tandem mass spectrometry after simple liquid–liquid extraction. This pharmacokinetic model of KAU was best described by a two-compartment model with first-order absorption. To identify efflux transporters involved in the absorption of KAU, a Caco-2 monolayer model was used. Estimated PK parameters were: systemic clearance, 23.89 L/h; inter-compartmental clearance, 15.55 L/h; rate constant for absorption, 1.72 h−1; volume of distribution of the central compartment, 24.44 L; and volume of distribution of the peripheral compartment, 64.05 L. Results from Caco-2 bidirectional transport study suggested that KAU was a potential substrate of efflux transporters. In summary, PKs of KAU were successfully characterized after administration of a usual dose of Araliae continentalis Radix extract powder in human with the newly developed bioanalytical method and the mechanism of absorption of KAU was identified clearly.
Highlights
Aralia continentalis Kitagawa has been extensively cultivated in Asia, Siberia, China, and Korea
Clinical usual dose of 1.0054 g Araliae continentalis Radix extract powder containing 1.147 mg of Kaurenoic acid (KAU) was orally administrated to humans
Gasparetto et al [25] reported kinetic profiles of Main Guaco metabolites using syrup formulation after 60 mL Guaco syrup containing 8.9 mg of KAU was administered to humans
Summary
Aralia continentalis Kitagawa has been extensively cultivated in Asia, Siberia, China, and Korea. In Korea, Araliae continentalis Radix extract powder has been approved by the Ministry of Food and Drug Safety (MFDS) Kaurenoic acid (KAU) is one of the representative diterpenes isolated from Aralia continentalis It possesses various biological activities, including anticonvulsant [8], tumor suppression [9], leukemia apoptosis [10], and anti-inflammatory. Isolation of KAU from other herbs such as Mikania glomerata [17], Copaifera langsdorffii [18], Sphagneticola trilobata [19], Pseudognaphalium vira vira [12], and several Annonaceae families [8,20,21,22] has been reported In spite of these therapeutic uses, KAU has to be used carefully because of its toxic effect. Cavalcanti et al [20] has identified its genotoxic and mutagenic effects in human leukocytes, yeast, and mice tissue cells
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