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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。
Objective To study the pharmacokinetics of CsA in type 1 diabetic rats. Methods Rats with type 1 diabetes were established by intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg · kg -1. After 5 weeks of modeling, the rats in diabetic group and normal control group were given 10 mg · kg -1 body weight of Cs A 1 μL · g -1 body weight, Pharmacokinetics. CsA concentration in whole blood was detected by enzyme immunoassay. Results After 1 week of STZ injection, the fasting blood glucose of rats exceeded 11.1 mmol·L -1, confirming the successful modeling of type 1 diabetic rats. After 5 weeks of modeling, the total cholesterol and triglyceride were significantly increased in diabetic rats except blood sugar. After administration of Cs A, the concentration-time curve of Cs A in diabetic rats was different from that of the normal control rats, presenting a bimodal phenomenon. The T max and C max of diabetic rats were lower than those of the normal control group, but the difference was not statistically significant. The T max of rats in normal control group and diabetic group were (3.3 ± 1.6) and (3.2 ± 2.5) h and (593 ± 104.8) ng · m L ~ (579.0 ± 208.5) and (-1). The AUC0-24h and t1 / 2 of CsA decreased significantly in diabetic rats, which were respectively 51% and 70% of those in normal control rats. The AUC0-24h of rats in normal control group and diabetic rats were (7343.2 ± 2333.7), (3729.7 ± 1106.6) ng · m L ~ (-1), t1 / 2 were (8.5 ± 1.5) and (6.0 ± 0.9) h, respectively. Conclusions The pharmacokinetics of CsA administered to rats with type 1 diabetes mellitus are significantly changed, suggesting that the rational use of CsA in patients with diabetes mellitus should be paid attention to.