益母草碱在大鼠体内的药动学研究

Pharmacokinetics of leonurine in rats

目的 研究益母草碱在大鼠体内的药动学。方法 建立了测定大鼠血浆中益母草碱的高效液相色谱法 ,色谱条件为AlltechC18色谱柱 (2 5 0mm× 4.6mm ,5 μm) ,流动相 :甲醇 水 二乙胺 (75∶2 5∶0 .75 ) ,流速 :1mL·min-1,检测波长 :2 82nm。从股静脉注射益母草碱溶液 ,测定不同时间的血药浓度。用 3P87药动学程序对血药浓度 时间数据进行拟合。结果 大鼠静注益母草碱后 ,其主要的药动学参数为 :VC(0 .35 3± 0 .0 2 3)L·kg-1,CL(0 .45 1± 0 .0 74)mg·h-1·kg-1,K12 (7.787± 2 .2 10 )h ,K2 1(0 .887± 0 .32 9)h-1,Ke(1.2 76± 0 .182 )h-1,t1/2α(0 .0 74± 0 .0 2 0 )h ,t1/2 β(6 .32± 1.35 )h ,曲线下面积AUC(6 .2 0±0 .47) μg·h·mL-1。结论 益母草碱在大鼠体内呈二室内开放模型 ,进入体内迅速分布 ,而代谢消除比较缓慢 ,其生物半衰期超过 6h。

OBJECTIVE: To study the pharmacokinetics of leonurine, a major alkaloid in the crude drug of Yimu Cao, in rats. METHODS: A HPLC method for the determination of leonurine in serum was establised. The chromatographic condition included Alltech C18 column (250 mm × 4.6 mm, id, 5 μm), the mobile phase consisting of CH3OH-H2O-(C2H5) NH2(75:25:0.75), the flowe rate at 1 mL&middotmin-1, the detective wavelength at 282 nm. Leonurine was injected into the rats through thigh vein, and its concentrations at different times were determined. The data were processed with the software 3P87. RESULTS: The primary pharmacokinetic parameters were: VC(0.353 ± 0.023) L&middotkg-1, CL(0.451 ± 0.074) mg&middoth-1&middotkg-1 K12 (7.787 ± 2.210) h-1, K21 (0.887 ± 0.329) h-1, Ke(1.276 ± 0.182) h-1, t1/2α (0.074 ± 0.020) h, t1/2β (6.32 ± 1.35) h, AUC (6.20 ± 0.47) μg&middoth&middotmL-1,respectively. CONCLUSION: The metabolism of leonurine in rats fited to 2-compartment model. The alkaloid distributed quickly but eliminated slowly. Its biological half-life was more than 6 hours.