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Objective:To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate(ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction(茵陈蒿汤,YCHD) using an ultra pressure liquid chromatography(UPLC) method.Methods:Rats were divided into a normal group and a model group,after modeled by 4%ANIT(75 mg/kg) for 48 h,they were orally administrated with YCHD extract at the dose of 0.324 g/kg,and then blood was collected from their orbital sinus after different intervals.Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase(ALT),aspartate aminotransferase(AST)]and bilirubins[total bilirubin(TBIL),direct bilirubin(DBIL)],the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC,and the pharmaceutical parameters were calculated with DAS2.1.1 software.Results:The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained.Their time to maximum plasma concentration(t_(max)) were both 0.25 h,the maximum concentration(C_(max)) were 4.533μg/mL and 6.885μg/mL, and their area under concentration-time curve(AUC)_(0→24h) were 16.272 and 32.981,respectively.There was a 51.88%and 100.46%increase in C_(max) and AUC_(0-t)(P<0.05),but there showed a 45.52%and 92.93%reduction in clearance of drug and volum of distribution(P<0.05),respectively.Conclusions:Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD,the absorption and distribution process was accelerated in liver injured rats,but the metabolism and elimination process was slowed.And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.
Objective: To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT) -induced experimental hepatic injury after oral administration of Yinchenhao Decoction using an ultra pressure liquid chromatography (UPLC) method. Methods: Rats were divided into a normal group and a model group, after modeled by 4% ANIT (75 mg / kg) for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g / kg , and then blood was collected from their orbital sinus after different intervals. Change in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL), direct bilirubin (DBIL)], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS 2.1.1 software. Results: The concentration-time curve of both normal and modeled rats after oral administration of YCH The maximum concentration (C_ (max)) were 4.533 μg / mL and 6.885 μg / mL, and their area under concentration-time curve ( AUC) _ (0 → 24h) were 16.272 and 32.981, respectively. There were 51.88% and 100.46% increase in C max and AUC 0-0 (P <0.05), but there was a 45.52% and 92.93 % reduction in clearance of drug and volum of distribution (P <0.05), respectively.Conclusions: Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats , but the metabolism and elimination process was slowed. And this this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.