【摘要】：目的研究環(huán)孢素(Cs A)在1型糖尿病大鼠體內(nèi)的藥代動(dòng)力學(xué)。方法大鼠腹腔注射65 mg·kg~(-1)鏈脲菌素(STZ)建立1型糖尿病大鼠模型。造模5周后,糖尿病組和正常對(duì)照組大鼠按10 mg·kg~(-1)體重灌胃給予Cs A 1 0μL·g~(-1)體重,比較2組大鼠灌胃后的藥代動(dòng)力學(xué)。通過(guò)酶擴(kuò)大免疫分析法檢測(cè)全血中的Cs A濃度。結(jié)果STZ注射1周后,大鼠空腹血糖超過(guò)11.1mmol·L~(-1),確認(rèn)1型糖尿病大鼠造模成功。造模5周后,除血糖外,糖尿病大鼠的總膽固醇及三酰甘油均顯著增高。灌胃Cs A后,糖尿病大鼠體內(nèi)Cs A的血藥濃度-時(shí)間曲線與正常對(duì)照組大鼠不同,呈現(xiàn)雙峰現(xiàn)象。糖尿病大鼠的T_(max)和C_(max)均低于正常對(duì)照組,但差異無(wú)統(tǒng)計(jì)學(xué)意義。正常對(duì)照組和糖尿病組大鼠的T_(max)分別為(3.3±1.6),(3.2±2.5)h,C_(max)分別為(579.0±208.5),(453.0±104.8)ng·m L~(-1)。Cs A在糖尿病大鼠體內(nèi)的AUC0-24h和t1/2顯著降低,分別為正常對(duì)照組大鼠的51%,70%,正常對(duì)照組大鼠和糖尿病組大鼠的AUC0-24h分別為(7343.2±2333.7),(3729.7±1106.6)h·ng·m L~(-1),t1/2分別為(8.5±1.5),(6.0±0.9)h。結(jié)論 1型糖尿病大鼠灌胃Cs A的藥代動(dòng)力學(xué)發(fā)生顯著改變,提示臨床應(yīng)注意Cs A在糖尿病患者中合理用藥問(wèn)題。
[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 鹵1.6), (3.2 鹵2.5) h and (579.0 鹵208.5) h, respectively. The AUC0-24h and T1 鈮，

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