Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection
Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection
复制标题
高脂饮食联合注射链脲佐菌素诱导糖尿病大鼠维拉帕米的药代动力学
DOI：
10.3109/00498254.2011.558933
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发表时间：
2011-06-01
期刊：
影响因子：
1.8
通讯作者：
Liu, X. D.
中科院分区：
文献类型：
--
作者：
Chen, G. M.;Hu, N.;Liu, X. D.
1.本研究旨在探讨2型糖尿病对维拉帕米静脉给药后药动学的影响.采用链脲佐菌素（STZ）和高脂饲料（HFD）联合诱导糖尿病（DM）大鼠模型。在DM大鼠、喂食HFD的大鼠和对照（CON）大鼠中，静脉内给予1 mg/kg维拉帕米后，测定维拉帕米的血浆浓度，并估计相应的药代动力学参数。DM大鼠血浆浓度下面积显著小于CON大鼠.体外微粒体研究表明，糖尿病大鼠维拉帕米的内在清除率明显高于对照组。与CON大鼠相比，在HFD大鼠中也观察到更高的固有清除率。Western blot结果显示，DM和HFD大鼠的CYP 3A 2水平较高，这与CYP3A.4的活性一致。提示糖尿病可增强维拉帕米在大鼠体内的代谢，这种增强作用可能与CYP 3A的诱导有关。
1. The aim of this study was to investigate effects of type 2 diabetes on the pharmacokinetics of verapamil after intravenous administration.2. Diabetes mellitus (DM) rats were induced by combination of high-fat diet (HFD) and streptozotocin. Plasma concentrations of verapamil in DM rats, rats fed with HFD, and control (CON) rats were measured after intravenous administration of 1 mg/kg verapamil and corresponding pharmacokinetic parameters were estimated. Area under the plasma concentration in DM rats was significantly smaller than that in CON rats.3. In vitro microsomal study showed that intrinsic clearance of verapamil in DM rats was significantly higher than those in CON rats. Compared to CON rats, higher intrinsic clearance was also observed in HFD rats. Western blot results demonstrated higher levels of CYP3A2 in DM and HFD rats, which was in line to activity of CYP3A.4. All the results gave a conclusion that diabetes may enhance metabolism of verapamil in rat, and the enhancement may partly result from induction of CYP3A.