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.