Zeng Yingtong, Xie Xingqian, Duan Jingjing, Zhou Ting, Zhang Ye, Yang Min, Xu Feng
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Sci Rep. 2014 Jan 21;4:3794. doi: 10.1038/srep03794.
Many diabetic patients complicated with wild to severe depression. It is unclear in diabetic medication whether depression perturbs the drug metabolic process of the hypoglycemic agents or not. The present study was designed to investigate the impact of chronic unpredicted mild stress (CUMS) -induced depression on mitiglinide (MGN) pharmacokinetics in rats. Adult female Sprague-Dawley rats in CUMS group were subjected to different types of stressors and the stress procedures lasted for 8 weeks. Control group without receiving stress had free access to food and water. Open-field test and 5-HT levels were assayed to evaluate the depression. After CUMS all rats were given 2.5 mg/kg of mitiglinide per os. The blood samples were collected at different time and mitiglinide plasma concentration was measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Non-compartmental statistical moment analysis was processed with DAS software. In CMUS-induced depression group, peak concentration (Cmax), peak time (Tmax), area under curve (AUC0 → ∞), mean residence time (MRT0 → ∞), and half-life (T1/2z) were reduced while total plasma clearance (CLz/F) was increased compared to control group. These preliminary results indicated that CUMS-induced depression alter the drug metabolic process of mitiglinide in rats. This finding will be significant in clinic.
许多糖尿病患者并发了从轻度到重度的抑郁症。在糖尿病药物治疗中，抑郁症是否会干扰降糖药物的代谢过程尚不清楚。本研究旨在探讨慢性不可预测轻度应激（CUMS）诱导的抑郁症对大鼠米格列奈（MGN）药代动力学的影响。CUMS组的成年雌性Sprague-Dawley大鼠接受不同类型的应激源，应激程序持续8周。未接受应激的对照组可自由获取食物和水。通过旷场试验和5-羟色胺水平测定来评估抑郁情况。CUMS处理后，所有大鼠经口给予2.5mg/kg米格列奈。在不同时间采集血样，采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定米格列奈血浆浓度。使用DAS软件进行非房室统计矩分析。与对照组相比，在CUMS诱导的抑郁症组中，峰浓度（Cmax）、达峰时间（Tmax）、曲线下面积（AUC0→∞）、平均驻留时间（MRT0→∞）和半衰期（T1/2z）降低，而血浆总清除率（CLz/F）增加。这些初步结果表明，CUMS诱导的抑郁症改变了大鼠米格列奈的药物代谢过程。这一发现将在临床上具有重要意义。
