大鼠灌服雄黄后血浆中活性硫药动学及雄黄排泄研究

Determination of Reactive Sulfur in Rats Plasma and Its Pharmacokinetic Study after Administration of Realgar

目的：测定大鼠灌服雄黄后血浆中活性硫的药动学特征及雄黄的排泄规律。方法：采用高效液相色谱法测定大鼠灌胃给予（0. 5 g/kg）雄黄后活性硫的药动学参数;采用显微定量法测定雄黄的排泄规律。结果：灌胃给予大鼠雄黄0. 5 g/kg,血浆中活性硫的达峰浓度为（3. 23±0. 2）μmol/L,达峰时间为180 min,消除半衰期为（363±78） min,AUC0-∞为（1638±456） ng·h·m L^-1,灌胃48 h后雄黄总排泄率为89. 6%。结论：雄黄中的硫可作为活性硫供体,引起血浆中活性硫水平的改变;雄黄不能被机体完全吸收,大部分以原型形式排出体外。

Objective： To study the pharmacokinetic profile of reactive sulfide and excretion of realgar in feces in rats after oral administration of realgar. Method： A high performance liquid chromatography（ HPLC） coupled with precolumn derivatization method was established for the determination of plasma reactive sulfur and applied in the pharmacokinetic study of reactive sulfur in rats after administration of 0. 5 g/kg realgar. Microscopic quantitative method was first applied for the measurement of excretion of realgar in feces. Results： The time-course pharmacokinetics parameters were as follows： Cmax（3. 23 ± 0. 2） μmol/L,tmax180 min and t1/2（363 ± 78） min,AUC0-（1638 ± 456） ng·h·m L-1. The excretion rate of realgar was calculated to be 89. 6% in feces 48 hours after administration. Conclusion： Realgar has reactive sulfide and it can be used as the sustained release donor of sulfide. Most of realgar was excreted in feces by primary form.