Perturbation of mitiglinide metabolism by chronic unpredicted mild stress in rats.
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.
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Yingtong
Y
Zeng
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Xingqian
X
Xie
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Jingjing
J
Duan
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Ting
T
Zhou
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Ye
Y
Zhang
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Min
M
Yang
Sixth People's Hospital South Campus, Shanghai Jiaotong University, Shanghai, 201400, China.
Feng
F
Xu
D000818:Animals; D002853:Chromatography, Liquid; D003863:Depression / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D054833:Isoindoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D013315:Stress, Psychological / Q000097:blood / Q000473:pathology; D053719:Tandem Mass Spectrometry
D007004:Hypoglycemic Agents; D054833:Isoindoles; C087255:mitiglinide