Pharmacokinetics and tissue distribution evaluation of α-asaronol and its main metabolite in rats by HPLC method

Abstract

α-Asaronol is one of trace metabolites of α-asarone formed in vivo and in vitro and exhibits good anticonvulsant activities with low neurotoxicity. The present study was mainly to describe the pharmacokinetics and tissue distribution of α-asaronol and its metabolite E-2,4,5-trimethoxy cinnamic acid (E-2,4,5-TMCA), in rat after oral and intravenous administration of α-asaronol. The results indicate that α-asaronol can be absorbed (t_max = 5-10 min) and transformed to E-2,4,5-TMCA (t_max = 10-15 min) rapidly after oral administration. Presumably due to hepatic first-pass effect, α-asaronol shows a low bioavailability (about 25.9%). Furthermore, α-asaronol is distributed rapidly and widely in various tissues with the order of brain > heart > kidney > spleen > liver > lung, and eliminated quickly following the intravenous administration. The maximal concentration of α-asaronol in the brain is about 1.603 ± 0.221 μg/g at 5 min. In comparison, the concentrations of E-2,4,5-TMCA, except brain, are all higher than that of α-asaronol in the tested tissues with the order of kidney > liver > lung > heart ≈ spleen > brain. Current study results will contribute to interpretation and understanding preclinical PK properties of α-asaronol and its antiepileptic effects in animals.

Keywords: HPLC; Metabolites; Pharmacokinetics; Tissue distribution; α-Asaronol.