The Preliminary Study On The Hepatic Uptakemolecular Mechanism Of Isorhynchophylline

Objective:The purpose of this study was to determine whether there is saturated enzymes or transporters involved in drug absorption and excretion by analying the pharmacokinetici s parameters of rhynchophyllin as well as investigate the role of Octs and Oatps in the hepatic uptake process of isorhynchophylline in vivo by using rats pretreated by Octs and Oatps inhabitors.Methods:The plasma concentrations of isorhynchophylline in mice after iv administration at dose of 40 m·kg^-1,20 mg·kg1,4 mg·kg^-1 were determined at different time points（15,90,120,180,300min）,and then the pharmacokinetic parameters were analyzed by 3P97software.Isorhynchophyllie was administered at aloading dose of 40mg·kg^-1,followed by constant infusionat 4μL·h-1·g^-1 for 5h to rats pretreated with/without rifampicin/corticosterone.Blood and liver samples were collected 300min.The plasma concentrations of isorhynchophyllie in liver and blood was determined by HPLC.Results:The results of this study support dose-dependent pharmacokinetic characteristics of isorhynchophylline ranging from 20 mg·kg^-1 to 40 mg·kg^-1 by analyzing the pharmacokinetic parameters such as K21,K12,t1/2.The parameters of AUC0-∞ were not significantly correlated with three dosages.After administrated by Oatps inhibitors,The Kp values of isorhynchophylline were decreased comparing with the Kp of the control group,but the reduction was not obvious as the Kp of the group pretreated by Octs inhibitors.Conclusions:Inconclusion,the present findings suggest that Octs as well as Oatps are responsible for the hepatic uptake of isorhynchophylline,whereas Octs play a more important role than Oatps in the process of transport.