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

• Published in: Journal of pharmaceutical and biomedical analysis 2019-08, Vol.172, p.349-356
• Main Authors: Sun, Ying, Bai, Yajun, Zeng, Min, Chen, Xufei, Xie, Jing, Li, Bin, He, Xirui, Bai, Yujun, Jia, Pu, Meng, Xue, Liang, Jing, Wang, Shixiang, Fan, Tai-Ping, Wu, Biao, Zheng, Xiaohui
• Format: Article
• Language: English
• Subjects: Administration, Intravenous - methods; Administration, Oral; Animals; Anisoles - pharmacokinetics; Anticonvulsants - pharmacokinetics; Biological Availability; Chromatography, High Pressure Liquid - methods; HPLC; Injections, Intravenous - methods; Male; Metabolites; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Tissue distribution; Tissue Distribution - physiology; α-Asaronol
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2019.05.004

[Display omitted] •α-Asaronol is one of trace metabolites of α-asarone or Acorus tatarinowii and exhibits good antiepileptic activity in animals.•A rapid and sensitive HPLC method was developed for the simultaneous determination of α-asaronol and its metabolite 2,4,5-TMCA in rat plasma and tissues.•It is the first report on pharmacokinetics and tissue distribution of α-asaronol and 2,4,5-TMCA after oral and intravenous administration of α-asaronol in rats.•This investigation would be helpful for further studying pharmacology and structural modification of α-asaronol. 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 (tmax = 5–10 min) and transformed to E-2,4,5-TMCA (tmax = 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.