Comparison between the pharmacokinetics of meranzin hydrate in a rat model of chronic depression and in controls following the oral administration of Chaihu-shugan-san

Abstract

Previous studies have shown that meranzin hydrate (MH) may be beneficial in depressive disorders. However, to the best of our knowledge, the pharmacokinetic characteristics of MH in depression have not previously been investigated. Chronic mild stress (CMS) in rats is used as a model of depression. The present study was designed to evaluate and compare the pharmacokinetics of MH in CMS and control rats following the oral administration of Chaihu-Shugan-San (CSS). Rats were randomly divided into CMS and control groups and blood samples were obtained following the oral administration of CSS. The quantification of MH levels in the plasma for pharmacokinetic study was achieved using a simple and rapid ultra-performance liquid chromatography with photodiode array (UPLC-PDA) method. Following the oral administration of CSS to CMS rats and controls, the maximum plasma concentration (Cmax) of MH was 58.66±6.64 and 57.54±12.67 ng/ml at 108.00±26.83 and 54.00±8.22 min, respectively. Compared with the value of the area under the concentration-time curve (AUC)0-1440 in control rats (19,896.76±1,041.95 μg·min/l), the AUC0-1440 value was reduced in CMS rats (18,401.32±4332.65 μg·min/l). There were no significant differences in the majority of the pharmacokinetic parameters of MH, including the values for Cmax, AUC0-1440, clearance rate (CL/F) and mean residence time (MRT0-1440), between the CMS rats and the controls. However, the pharmacokinetic parameters showed that CMS accelerated the absorption of MH in rats following the oral administration of CSS.