[1]胡 楠,王 欣,鲁晓雨,等.硝苯地平在链脲佐菌素诱导的糖尿病大鼠体内的药物代谢动力学[J].中国药理学通报,2018,(10):1461-1465.[doi:10.3969/j.issn.1001-1978.2018.10.026]
 HU Nan,WANG Xin,LU Xiao-yu,et al.Pharmacokinetics of nifedipine in diabetic rat model induced by streptozotocin[J].Chinese Pharmacological Bulletin,2018,(10):1461-1465.[doi:10.3969/j.issn.1001-1978.2018.10.026]
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硝苯地平在链脲佐菌素诱导的糖尿病大鼠体内的药物代谢动力学()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年10期
页码:
1461-1465
栏目:
论著
出版日期:
2018-10-26

文章信息/Info

Title:
Pharmacokinetics of nifedipine in diabetic rat model induced by streptozotocin
文章编号:
1001-1978(2018)10-1461-05
作者:
胡 楠1王 欣2鲁晓雨3赵 娣3王莉英1邹素兰1
1.常州市第一人民医院药剂科,江苏 常州 213003; 2.中国药科大学药学院,江苏 南京 211198; 3.中国药科大学基础医学与临床药学学院,江苏 南京 211198
Author(s):
HU Nan1 WANG Xin2 LU Xiao-yu3 ZHAO Di3 WANG Li-ying1 ZOU Su-lan1
1.Dept of Pharmacy, the First People's Hospital of Changzhou, Changzhou Jiangsu 213003, China; 2.School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; 3.School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
关键词:
糖尿病 链脲佐菌素 大鼠 硝苯地平 药物代谢动力学 CYP3A
Keywords:
diabetes streptozotocin rats nifedipine pharmacokinetics CYP3A
分类号:
R-332; R322.47; R345.99; R587.1; R972.3; R972.4
DOI:
10.3969/j.issn.1001-1978.2018.10.026
文献标志码:
A
摘要:
目的 研究硝苯地平在链脲佐菌素诱导的糖尿病大鼠体内的药物代谢动力学。方法 大鼠腹腔注射65 mg·kg-1链脲佐菌素(STZ)建立糖尿病大鼠模型。造模35 d后,检测糖尿病组大鼠和正常对照组大鼠的生理生化指标,并比较两组大鼠灌胃硝苯地平(10 mg·kg-1)后的药物代谢动力学; LC-MS/MS法检测血浆中硝苯地平的浓度,并用WinNonlin软件计算药动学参数; real-time PCR和Western blot法分别考察两组大鼠肝脏中CYP3A1 mRNA和蛋白表达水平。结果 STZ造模35 d后,模型组大鼠呈明显的三多一少的糖尿病症状,血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平均明显增加。灌胃硝苯地平后,糖尿病大鼠体内硝苯地平各时间点的血药浓度均低于对照组大鼠。硝苯地平在糖尿病组、对照组大鼠的Cmax分别为(2295.00±875.00)μg·L-1、(3875.00±720.24)μg·L-1,Tmax分别为(0.83±0.61)h、(0.50±0.16)h,AUC0-t分别为(8377.54±2148.57)μg·h·L-1、(18072.42±2456.72)μg·h·L-1,T1/2分别为(2.41±0.62)h、(2.81±1.16)h。与对照组相比,糖尿病大鼠肝脏中CYP3A1 mRNA和蛋白表达均明显增加。结论 硝苯地平在糖尿病大鼠体内的药代动力学发生明显改变,提示临床注意硝苯地平在糖尿病患者中安全、合理用药问题。
Abstract:
Aim To investigate the effect of diabetes mellitus induced by streptozotocin(STZ)on oral pharmacokinetics of nifedipine in rats.Methods Diabetic rats were induced by intraperitoneal administration of 65 mg·kg-1 STZ.The physiological and biochemical parameters of diabetic and normal rats, as well as the pharmacokinetics of nefidipine after oral administration of nefidipine(10 mg·kg-1)were compared between two groups on 35th day after STZ injection.Plasma concentration of nifedipine was measured by a LC-MS/MS method, and the pharmacokinetics parameters were calculated by WinNonlin software.The hepatic CYP3A1protein expression and mRNA level were determined by Western blot and QT-PCR method, respectively.Results Rats in diabetic group showed obvious symptom of polyuria, polydipsia, overeating and emaciation after 35 days of induction.Blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol levels significantly increased in diabetic rats compared with normal rats.The concentrations of nifedipine in diabetic rats at each time point were all lower than those in normal rats.The Cmax of nifedipine in diabetic and normal rats was(2295.00±875.00)μg·L-1 and(3875.00±720.24)μg·L-1, respectively, Tmax was(0.83±0.61)h and(0.50±0.16)h, respectively, AUC0-t was(8377.54±2148.57)μg·h·L-1 and(18072.42±2456.72)μg·h·L-1, respectively, and T1/2 was(2.41±0.62)h and(2.81±1.16)h, respectively.Compared with normal rats, the CYP3A1 protein expression and mRNA levels were significant higher in liver of diabetic rats.Conclusion The pharmacokinetics of nifedipine after oral administration were significantly changed in diabetic rat model compared to normal controls, which should be taken into consideration in clinical medication.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期:2018-06-14,修回日期:2018-07-24
基金项目:国家自然科学基金资助项目(No 81503136)
作者简介:胡 楠(1986-),女,博士,副主任药师,研究方向:药物代谢动力学与临床药学,E-mail:hn_324@163.com;
邹素兰(1966-),女,主任药师,副教授,研究方向:临床药学,通讯作者,E-mail:zsl661104@163.com
更新日期/Last Update: 2018-08-26