Preliminary Study On Molecular Pharmacokinetic Mechanisms Of Gastrodia Elata And Uncaria In Liver Uptake And Elimination

Aim:Preliminary study on molecular pharmacokinetic mechanisms of Gastrodia elata and Uncaria rhynchophylla in liver uptake and elimination.Methods:First of all,the rats were given isorhynchophylline/gastrodin,then intravenous injection of gastrodin/isorhynchtin,and the plasma concentration of gastrodin and the concentration of liver in different time points were determined by high performance liquid chromatography(HPLC),and comparing and analyzing the ratio of liver drug concentration to blood concentration ratio(Kp value)between experimental group and control group(direct intravenous injection of gastrodin/isorhynchophylline).In order to study the molecular pharmacokinetic mechanism of Gastrodia elata and Uncaria rhynchophylla in liver uptake.Secondly,used "Cocktail"probe drug method to giving rats a series of micro-probe drugs at the same time(theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide,dextromethorphan),then collected blood after 5min,15min,30min,1h,2h,3h,5h,6h,12h,24h.Established a HPLC method to detection of 6 kinds of probe drug concentration in rat blood at the same time,calculated and compared the pharmacokinetic parameters of the probes between experimental group and control group,to illuminated the effects of Gastrodia elata,Uncaria rhynchophyllum and the couplet medicines to the metabolic activity of CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6.In order to study the molecular pharmacokinetic mechanism of Gastrodia elata and Uncaria rhynchophylla in liver elimination.ResuLts:1)Kpgastrodin<Kpgastrodin+isorhynchophylline,illustrated that the process of gastrodin from blood uptake to the liver was promoted after given isorhynchophylline;Kpisorhynchophylline<Kpisorhynchophylline+gastrodin,illustrated that the process of isorhynchophylline from blood uptake to the liver was inhibition after given gastrodin.2)Established a HPLC method to detection of 6 kinds of probe drug concentration in rat blood at the same time(gradient elute,multiple wavelength detection at the same time),it was proved that the method had good stability and high precision.3)There was no significant difference in the Gastrodia elata group and the control group,the result showed that Gastrodia elata had no significant effect on the six main subtypes of CYP450;Between Uncaria rhynchophylla group and control group,the AUC of dapsone and orinase was reduced,t1/2 was reduced and CL was increased.The result showed that the activity of CYP3A4 and CYP2C9 was increased;Between couplet medicines group and control group,the AUC of dapsone and orinase was reduced,t1/2 was reduced and CL was increased,and the AUC of chlorzoxazone was increased,t1/2 was increased and CL was reduced,The result showed that the activity of CYP3A4 and CYP2C9 was increased and the activity of CYP32E1 was reduced.Conclusion:l)Gastrodin might be an inhibitor of isorhynchophylline in rat liver uptake.2)Isorhynchophylline might be an inducer of gastrodin in liver uptake.3)Gastrodia elata had no significant effect on the six main subtypes of CYP450.4)The couplet medicines of Gastrodia elata and Uncaria rhynchophylla might have inhibitory effect on CYP2E1,and might have effect on CYP3A4 and CYP2C9.