The Preliminary Study On The Hepatic Uptake Molecular Mechanism Of Gastrodia

Aim:To estimate the pharmacokinetics characteristics of Gastrodin in mice;determine the usage and dosage of the broad-spectrum inhibitors of organic anion transporting polypeptides(Oatps)and organic cation transporters(Octs)in vivo;explore the hepatic uptake molecular mechanism of Gastrodia in rats.Methods:Mice were injected intravenously with three different doses of Gastrodia,and then detected the plasma concentration of each time points by HPLC.The pharmacokinetic were calculated by 3P97,in order to determine the pharmacokinetics characteristics of Gastrodin in mice.Rats were given the Oatps and Octs inhibitors in the first the specific substrate of Oatps and Octs was then injected intravenously.By detecting the specific substrate blood and hepatic drug concentration at each time points,the changes of Kp(CT,SS/CB,SS)were compared to determine the Oatps and Octs inhibitors and the usage and dosage.Rats were also given the Oatps and Octs inhibitors in the first,but Gastrodin was then injected intravenously.The concentration of Gastrodin in blood and hepatic were tested.The molecular mechanism of hepatic transport was preliminarily estimated by compare the Kp value.ResuLts:With the increasing of dosage,there is no correlation between the AUC(area under the curve)and dose.And the half life also increased.These results all showed that the pharmacokinetic of Gastrodin was nonlinear.After Oatps and Octs inhibitors were administered to rats,the Kp values of the specific substrates were significantly lower than blank control group(P<0.05).So the usage and dosage of Oatps and Octs inhibitors was feasible.After given the Oatps and Octs inhibitors,Gastrodin was then injected intravenously.Results showed that the Kp value was significantly lower than blank control group(P<0.05).ConcLusion:The pharmacokinetic characteristics of Gastrodin was nonlinear;The hepatic uptake of Gastrodin is mainly related to the Oatps and Octs.And the Kp(Octs inhibitor)<Kp(Oatps inhibitor)<Kp blank,also show that Gastrodin is the substrate of Oatps and Octs,and the affinity of Octs is greater than Oatps.