Evaluation Of Impacts Of Magnesium Isoglycyrrhizinate On Rat Hepatic Cytochrome P450Enzymes By Cocktail Probe Drugs

Aim of the study: The purpose of this study was to investigate the in vivo effect ofMagnesium Isoglycyrrhizinate injection on rat cytochrome P450enzymes(CYP3A4、CYP2D6、CYP2C19、CYP1A2、CYP2E1、CYP2C9) and to assess its safety throughits potential interaction with co-administered drugs.Methods: Rats were divided into three groups randomly: control group, single dosegroup and multi-dose group.The probe drugs contained oprazole(10mg/kg),chlorzoxazone(50mg/kg),meclofenamic(5mg/kg),theophylline(25mg/kg),midazolam(10mg/kg),dextromethorphan(5mg/kg).Rats were intravenous administrated withMagnesium Isoglycyrrhizinate injection at the dose of20mg/kg. The probe drugswere injected to each rat using intraperitoneal injection. The MagnesiumIsoglycyrrhizinate injection were injected to each rat using tail vein injection.0.5mlblood samples were then drawn by retro-0rbital venous plexus puncture at definedtime points. The plasma concentrations of probe drugs were simultaneouslydetermined by HPLC. Pharmacokinetic parameters simulated by DAS2.0softwarewere used for the evaluation of Magnesium Isoglycyrrhizinate injection on theactivities of rat CYP3A4、CYP2D6、CYP2C19、 CYP1A2、CYP2E1、CYP2C9enzymes. The Student’s T test was used for further sample statistical analysis.Results: There was no significant influence of pharmacokinetic parameters oftheophylline, diclofenac,omeprazole and dextromethorphan on MagnesiumIsoglycyrrhizinate injected pretreated rats. But many pharmacokinetic parameters ofmidazolam and chlorzoxazone in Magnesium Isoglycyrrhizinate injection pretreatedrats were affected significantly (P <0.05).Conclusions: Magnesium Isoglycyrrhizinate injection was induced CYP2E1, andinhibited CYP3A4in vivo. In our study, the results suggested that MagnesiumIsoglycyrrhizinate injection showed no effects on rat CYP2D6、CYP1A2、CYP2C19 and CYP2C9. We should be cautious when Magnesium Isoglycyrrhizinate injectionwas used with the drug which metabolic by CYP2E1and CYP3A4.