李育卿(1987-),女,硕士,从事药物代谢动力学研究。电话:15009426240；E-mail:0544023@163.com。
目的 从格列本脲的药动学考察链脲佐菌素诱导糖尿病模型大鼠的适宜性。方法腹腔注射链脲佐菌素60 mg/kg诱发糖尿病大鼠模型, 与正常大鼠灌胃给予10 mg/kg格列本脲,采用高效液相色谱法分析其血药浓度。用DAS 2.0软件处理数据,计算药动学参数。结果格列本脲在正常大鼠和模型大鼠体内的药动学参数为:Tmax分别是84.784 min,255.427 min；Cmax分别是0.259 mg/L,0.910 mg/L；CL分别是0.092 L/min/kg,0.019 L/min/kg；AUC(0~720min)分别是509.523 mg/L·min,1528.280 mg/L·min。结论格列本脲在正常大鼠与糖尿病大鼠体内的药动学过程有显著性差异,但此结果与文献不一致,此模型可能不适合考察药物在II型糖尿病病态下的药动学研究。
Objective To explore whether streptozotocin-induced diabetic rat models are suitable to evaluate the pharmacokinetic processes of glibenclamide in the diabetic state. MethodsDiabetic rats induced by intraperitoneal injection of 60 mg/kg streptozotocin and normal rats were administered glibenclamide at a dose of 10 mg/kg. The concentration of glibenclamide was determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated using DAS 2.0 software. ResultsThe pharmacokinetic parameters of glibenclamide in normal rats were as following:Tmax was 84.784 min, Cmax was 0.259 mg/L, CL/F was 0.092 L/min/kg and AUC(0-720min) was 509.523 mg/L·min. The same parameters in diabetic rats:Tmax was 255.427 min, Cmax was 0.910 mg/L, CL was 0.092 L/min/kg and AUC(0-720min) 1528.280 was mg/L·min. ConclusionsThere were significant differences between pharmacokinetic values of normal and diabetic rats. The results were different from that reported in the literature. Therefore, streptozotocin-induced diabetic rat models might not be suitable for pharmacokinetic evaluation of drugs in type Ⅱ diabetic conditions.
李育卿,魏玉辉,周燕,张帆,王丹,武新安.格列本脲在糖尿病大鼠体内药动学评价[J].中国比较医学杂志,2012,(4):15~18,29.
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