环孢素在1型糖尿病大鼠体内的药代动力学  

Pharmacokinetics of cyclosporine in type 1 diabetic rat model

作　　者：蒋艳[1] 陈荣[1] 柳丽[2] 储奕[2] 唐颖娟 邹素兰[1] 胡楠[1] 

机构地区：[1]常州市第一人民医院药剂科,江苏常州213000 [2]常州大学制药与生命科学学院,江苏常州213000

出　　处：《中国临床药理学杂志》2017年第17期1665-1667,共3页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金青年基金资助项目(81503136);常州市卫生人才培养工程基金资助项目(2016CZBJ010)

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。Objective To investigate the pharmacokinetics of cyclosporine（CsA） in type 1 diabetes of rats. Methods Rats with type 1 diabetes were induced by intraperitoneal administration of 65 mg · kg-1 streptozotocin （STZ） . Pharmacokinetics of CsA （ 10 mg · kg-1 ） was compared between diabetic and normal rats on the 5 weeks after STZ in- jection. Concentration of CsA in whole blood was measured by enzyme - multiplied immunoassay technique. Results Type 1 diabetes rats were successfully induced as the fasting blood glucose levels exceeded 11.1 mmol · L-l after STZ injection for 1 week. Beside glucose, total cholesterol （TC） and triacylglyeerol （TG） in serum of diabetic rats were significantly higher than those in normal rats after STZ injection for 5 weeks. Unlike normal rats, the pharmacokinetics of CsA in diabetic rats exhibited a double peak after oral administration. The Tin= and C=x were lower in diabetic rats than normal rats, although without statistical differences as follows： T,xWaS （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） in normal and diabetic rats. Compared with normal rats, AUC and tm/2 of CsA in diabetic rats decreased significantly, which were 0. 51 and 0. 70 times those of normal rats, respectively; AUC was （ 7343.2 ± 2333.7 ）, （3729. 7 ± 1106. 6） h·ng·m L-（-1）,tl/2 was （8.5 ± 1.5 ）, （6.0 ± 0. 9） h in normal and diabetic rats. Conclusion The oral pharmacokinetics of CsA was significantly different in type 1 diabetic rat model compared to normal controls, which should be taken into consideration in clinical medication.

关 键 词：1型糖尿病 环孢素 药代动力学 酶扩大免疫分析法 

分 类 号：R979.5[医药卫生—药品]