环孢素在1型糖尿病大鼠体内的药代动力学

发布时间：2019-06-03 08:46

【摘要】：目的研究环孢素(Cs A)在1型糖尿病大鼠体内的药代动力学。方法大鼠腹腔注射65 mg·kg~(-1)链脲菌素(STZ)建立1型糖尿病大鼠模型。造模5周后,糖尿病组和正常对照组大鼠按10 mg·kg~(-1)体重灌胃给予Cs A 1 0μL·g~(-1)体重,比较2组大鼠灌胃后的药代动力学。通过酶扩大免疫分析法检测全血中的Cs A浓度。结果STZ注射1周后,大鼠空腹血糖超过11.1mmol·L~(-1),确认1型糖尿病大鼠造模成功。造模5周后,除血糖外,糖尿病大鼠的总胆固醇及三酰甘油均显著增高。灌胃Cs A后,糖尿病大鼠体内Cs A的血药浓度-时间曲线与正常对照组大鼠不同,呈现双峰现象。糖尿病大鼠的T_(max)和C_(max)均低于正常对照组,但差异无统计学意义。正常对照组和糖尿病组大鼠的T_(max)分别为(3.3±1.6),(3.2±2.5)h,C_(max)分别为(579.0±208.5),(453.0±104.8)ng·m L~(-1)。Cs A在糖尿病大鼠体内的AUC0-24h和t1/2显著降低,分别为正常对照组大鼠的51%,70%,正常对照组大鼠和糖尿病组大鼠的AUC0-24h分别为(7343.2±2333.7),(3729.7±1106.6)h·ng·m L~(-1),t1/2分别为(8.5±1.5),(6.0±0.9)h。结论 1型糖尿病大鼠灌胃Cs A的药代动力学发生显著改变,提示临床应注意Cs A在糖尿病患者中合理用药问题。
[Abstract]:Objective to study the pharmacokinetics of cyclosporine (Cs A) in type 1 diabetic rats. Methods the rat model of type 1 diabetes mellitus was established by intraabdominal injection of 65 mg kg~ (- 1) streptozotocin (STZ). After 5 weeks of modeling, the rats in the diabetic group and the normal control group were given Cs A 10 渭 L 路g ~ (- 1) body weight intragastrically at 10 mg kg~ (- 1) body weight, and the pharmacokinetics of the two groups was compared. The concentration of Cs A in whole blood was detected by enzyme expanded immunoassay. Results one week after STZ injection, the fasting blood glucose of rats exceeded 11.1mmol 路L ~ (- 1), which confirmed that the model of type 1 diabetic rats was successful. After 5 weeks of modeling, the total cholesterol and triacylglycerol in diabetic rats were significantly increased except blood glucose. After intragastric administration of Cs A, the blood concentration-time curve of Cs A in diabetic rats was different from that in normal rats, showing bimodal phenomenon. The T _ (max) and C _ (max) of diabetic rats were lower than those of normal control group, but the difference was not statistically significant. The T _ (max) and C _ (max) of normal control group and diabetic group were (3.3 卤1.6), (3.2 卤2.5) h and (579.0 卤208.5) h, respectively. The AUC0-24h and T1 鈮，

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