动物造模,肠易激综合征 z-bio 2022-12-09 385

　　Objective To determine the blood concentration of 10 active ingredients in Wuji pills at different time points after single and multiple oral administration, and compare their pharmacokinetic characteristics in normal rats and chronic visceral hypersensitive irritable bowel syndrome (CVH-IBS) rats.

　　Methods The rat model of CVH-IBS was established by colon balloon stimulation in neonatal rats, and the visceral sensitivity was evaluated. After single or multiple intragastric administration of Wuji pill extract, blood was collected from jugular vein at different time points. The plasma concentrations of 10 active components of Wuji pill in plasma were simultaneously detected by ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and their pharmacokinetic parameters were compared.

　　Results The visceral sensitivity of CVH-IBS rats was enhanced. Compared with single administration, the time to peak (tmax) of normal and model rats after multiple administration was earlier. The difference between the model and normal rats after single administration can positively verify the previous experimental results. Compared with normal rats after multiple administration, the peak plasma concentration (Cmax), area under the curve (AUC0-t), and total clearance (Cl) of the active ingredient of Wuji pills in the model rats changed significantly. The Cmax of berberine hydrochloride, berberine hydrochloride and epiberberine increased significantly, while the C0-t of palmatine hydrochloride, jatrorrhizine hydrochloride, dihydroberberine, evodiamine and rutaecarpolide decreased significantly; Berberine hydrochloride and epiberberine AUC0-t increased significantly, while palmatine hydrochloride, dihydroberberine, jatrorrhizine hydrochloride, evodiamine and rutaecarpolide AUC0-t decreased significantly; Berberine hydrochloride and rutaecarpolide Cl increased significantly, while epiberberine Cl decreased significantly. Palmatine hydrochloride and paeoniflorin t1/2 were significantly decreased, while jatrorrhizine hydrochloride Vd was significantly increased. Compared with single administration, the Cmax of berberine hydrochloride, jatrorrhizine hydrochloride, epiberberine hydrochloride and dihydroberberine in the active component of coptis chinensis was significantly reduced in the model rats after multiple administration: jatrorrhizine hydrochloride Cl was significantly reduced. The active ingredient of white peony, paeoniflorin t1/2, decreased significantly and Cl increased significantly.

　　Conclusion The pharmacokinetic behavior of the active components in Wuji Pill in normal rats, CVH-IBS rats and CVH-IBS rats at the later stage of Wuji Pill treatment is significantly different, which may be related to the metabolic function changes such as the intestinal barrier damage at the early stage of IBS treatment and the intestinal barrier repair at the later stage of treatment, the accumulation of drug hepatointestinal circulation, and the activity of liver enzymes.