异硫氰酸基雷公藤内酯醇活性代谢物雷公藤甲素在大鼠体内的药代动力学

Pharmacokinetics of triptolide as active metabolite of iso-tripthiocyanatolide in SD rats

目的观察大鼠单剂量静脉注射异硫氰酸基雷公藤内酯醇后雷公藤甲素的药代动力学。方法将大鼠分为2组(每组5只),分别单次尾静脉注射异硫氰酸基雷公藤内酯醇低、高剂量(4.25,8.50 mg·kg-1)。用LC-MS/MS法,检测大鼠血浆中雷公藤甲素的浓度,用BAPP 3.2软件计算药代动力学参数。结果低、高剂量的主要药代动力学参数如下:Cmax分别为(12.36±1.09),(55.74±21.20)ng·mL-1,Tmax均为(2.0±0.0)min,t1/2分别为(12.82±2.41),(13.73±2.84)h,AUC0-t分别为(245.93±42.50),(1034.45±471.76)ng·min.mL-1。结论在4.25～8.50 mg·kg-1,雷公藤甲素的药代动力学表现出非线性消除特征。

Objective To develop LC-MS/MS assay for determination of triptolide and to study its pharmacokinetics after iv iso-tripthiocyanatolide in SD rats.MethodsA sensitive LC-MS/MS method was validated and applied for the determination of triptolide plasma concentration in rats,and parameters of pharmacokinetics were calculated by BAPP 3.2 software.Results After intravenous administration of iso-tripthiocyanatolide to rats（4.25,8.50 mg·kg-1）,the main pharmacokinetic parameters were as follow：Cmax were（12.36±1.09）,（55.74±21.20） ng·mL^-1,Tmax were both（2.0±0.0） min,t1/2 were（12.82±2.41）,（13.73±2.84） h,AUC0-t were（245.93±42.50）,（1034.45±471.76） ng·min·mL^-1,respectively.ConclusionIn the range of 4.25-8.50 mg·kg-1 after iv triptisothiocyanatolide,triptolide appears to have nonlinear elimination profile.