芦丁在正常及糖尿病肾病大鼠体内药代动力学研究

目的比较芦丁在正常大鼠及糖尿病肾病大鼠体内药代动力学行为的差异。方法腹腔注射链脲霉素建立糖尿病肾病模型,静脉给予芦丁后取血分离血浆,采用HPLC-DAD法检测血浆中芦丁的浓度,以矩量法计算药代动力学参数。结果与正常大鼠比较,糖尿病肾病大鼠给予芦丁后体内AUC（0-4）明显增加〔（39.20±12.10）mg.h/L vs.（69.40±24.20）mg.h/L,P〈0.01〕、体内平均滞留时间显著延长〔（0.726±0.13）h vs.（1.069±0.17）h,P〈0.05〕、血浆消除半衰期显著增大〔（5.413±0.57）h vs.（6.595±0.38）h,P〈0.05〕、血浆清除率显著减小〔（0.424±0.071）L.h-1.kg-1vs.（0.226±0.072）L.h-1.kg-1,P〈0.05〕。结论芦丁在糖尿病肾病大鼠与正常大鼠之间存在明显的药代动力学差异。

Pharmacokinetic study of rutin in normal and diabetic nephropathy rats

Objective To investigate the difference in pharmacokinetic profiles of rutin in rats with diabetic nephropathy and normal ones. Methods The animal model of diabetic nephropathy was established by intraperitoneal injection （ip） of streptozotoein （STZ） in rats. Following intravenous administration of turin, blood samples were collected from the rats at the given time points to isolate plasma, which was assayed by HPLC - DAD method for the rutin concentration, and the pharmacokinetic parameters were analyzed by double - compartmental method （DAS2.0）. Results The comparison between the pharmacokinetic parameters of normal rats and those of the rats with diabetic nephropathy showed that there was a marked increase in AUC（0-4） ： （39.20 ± 12.10） mg · h/L vs. （69.40 ±24.20） mg · h/L （P 〈 0.01） ; prolonged mean retention time （MRT（0-4）） ： （0.726 ±0.13） h vs. （1.069±0.17） h （P〈0.05） ; significant increase in elimination 1/2 life （t1/2） ： （5.413 ±0.57） h vs. （6.595±0.38） h （P〈0.05） and markedly reduced plasma clearance （ Cl ） ： （ 0.424 ± 0.071 ） L · h · kg^-1 vs. （ 0.226 ± 0.072 ） L · h · kg^-1 （ p 〈 0.05 ）, respectively. Conclusion The results indicated that there were evident differences in pharmaeokinetic profiles of rutin between rats with diabetic nethropathy and normal ones.