Abstract:
BACKGROUND:Oxymatrine is one of the most promising alkaloids from Sophora flavescens for its excellent pharmacological effects. OBJECTIVE:The aim of this research is to assess the biopharmaceutical and pharmacokinetic activities of oxymatrine, and clarify its mechanisms of absorption and metabolism. METHODS:The biological characteristics of oxymatrine were systematically investigated by UHPLC-MS/MS. The mechanisms of absorption and metabolism of oxymatrine were further clarified through incubation in rat liver microsomes and transport across Caco-2 monolayer cell absorption model. RESULTS:It was found that the absolute oral bioavailability of oxymatrine was 26.43% and the pharmacokinetic parameters Cmax, Tmax, and t1/2 were 605.5 ng/mL, 0.75 h, and 4.181 h after oral administration, indicating that oxymatrine can be absorbed quickly. The tissue distribution tests showed that oxymatrine distributed throughout all the organs, with the small intestine accumulating the highest level followed by kidney, stomach and spleen. The Papp in Caco-2 cell line absorption model was over 1 × 10-5 and PDR 1.064, t1/2 of oxymatrine in rat liver microsome in vitro was 1.042 h, indicating that oxymatrine can be absorbed easily through passive diffusion and CYP450 enzymes could be involved in its metabolism. The plasma protein binding rate of oxymatrine was 2.78 ± 0.85%. CONCLUSION:Oxymatrine can be absorbed into blood easily through passive diffusion, mainly distributed in the intestine, stomach, liver and spleen in vivo, and CYP450 enzymes in liver could be involved in its metabolism.
journal_name
Curr Pharm Biotechnoljournal_title
Current pharmaceutical biotechnologyauthors
Wang HQ,Chen FH,Wang L,Chi LQ,Wang GHdoi
10.2174/1389201022666210118160529subject
Has Abstractpub_date
2021-01-18 00:00:00eissn
1389-2010issn
1873-4316pii
CPB-EPUB-113397pub_type
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