Pharmacokinetic Study Of Veratrilla Baillonii Franch And Aconitum Brachypodum Diels.

Veratrilla baillonii Franch（VBF）is a widely used anti-inflammatory drug for liver protection in clinic.When coadministered with Aconitum brachypodum Diels,VBF has synergistic anti-inflammatory and detoxication effects.To explore the vivo process of VBF,and clarify the mechanism of its hepatoprotective effect on Aconitum brachypodum Diels.from the perspective of pharmacokinetics,the following aspects were studied in this paper:Firstly,this experiment successfully established a sensitive and reliable analytical method of Ultra-High Performance Liquid Chromatography-Mass spectrometry（UPLC-MS/MS）,which was applied to the pharmacokinetics in rats under normal and pathological conditions after oral administration of gentiopicroside and water extracts of Veratrilla baillonii Franch（WVBF）.In addition,the relationship between plasma concentration-time-effect was established with AST and ALT in serum as pharmacodynamic indexes to analyze the correlation between pharmacokinetics and pharmacodynamics of WVBF in CCl₄-induced acute liver injury rats.The experimental results showed that the established UPLC-MS/MS method can simultaneously determine the contents of gentiopicroside（GPS）and sweroside（SW）in plasma.The method is rapid,reliable and reproducible,and the methodological verification meets the requirements of the guiding principles of biological sample analysis.Pharmacodynamic results showed that the increase of AST and ALT in WVBF and GPS treatment groups was obviously inhibited,pharmacokinetics results showed that the MRT_0-Tand AUC_0-Tvalues of gentiopicroside in WVBF groups were significantly higher than those of GPS standard drug administration groups,which indicated that other components contained in VBF could promote the absorption and distribution of GPS in vivo,resulting in the enhancement of the liver protection effect of GPS.What’s more,compared with the normal group administered with WVBF,the T_1/2and MRT_0-Twere longer,C_max、CL were shorten as well as AUC_0-Twere higher in the liver injury model groups（p<0.05）,which indicated that the absorptions of GPS and SW in liver injury rats accelerated,the absorption amounts increased,the elimination rates slowed down,and the residence time increased in vivo.Then,a new UPLC-MS/MS method was established to simultaneously determine the concentrations of aconitine（AC）and hypaconitine（HA）in rat plasma and tissues,and applied to study the pharmacokinetics and tissue distributions of rats treated with coadministration of WVBF and chloroform fraction of Aconitum brachypodum Diels.（CFA）.The experimental results showed that the established method can simultaneously detect the contents of AC and HA with good specificity and repeatability in plasma and tissues.Both AC and HA have good linear relationships in the ranges of 1-500 ng/m L in plasma and 5-1000 ng/m L in tissues.Pharmacokinetic tests showed that the T_1/2and MRT_0-Tof AC and HA in plasma were prolonged,C_maxand AUC_0-Twere decreased,and CL was increased after coadministration with VBF,has indicated that there was drug interaction between VBF and Aconitum brachypodum Diels.,which could reduce the exposure and accelerate the excretion rate of AC and HA in plasma.The results of tissue distribution showed that AC and HA were widely distributed in tissues of rats,and the contents of AC and HA in liver and kidney were higher than other tissues.However,after coadministration with VBF,the concentrations of AC and HA in spleen decreased at all time points.Spleen is an important digestive and absorption organ,which indicates that coadministration can reduce the absorption of drugs,and WVBF can alleviate the toxicity of CFA.