ABSTRACT
OBJECTIVE： To study the effects of berberine hydrochloride on the pharmacokinetics of tacrolimus in rats after single or multiple administration， and to provide reference for clinical combination therapy. METHODS： 30 rats were randomly divided into 5 groups， with 6 rats in each group： group one was treated with single administration of tacrolimus； group two was treated with tacrolimus intragastrically， twice a day， for consecutive 1 week； group three was treated with single administration of berberine hydrochloride， 5 min later given single administration of tacrolimus； group four was treated with tacrolimus intragastrically， twice a day， for consecutive 1 week， and then given tacrolimus intragastrically once 5 min after intragastric administration of berberine hydrochloride on the 8th day； group five was treated with berberine hydrochloride intragastrically， twice a day， and given tacrolimus intragastrically every 5 min， for consecutive 8 d. The doses of berberine hydrochloride and tacrolimus were 200 mg/kg and 0.945 mg/kg. The blood samples 0.3 mL were collected from posterior orbital venous plexus of rats 0， 5， 15， 30 min and 1， 2， 3， 4， 6， 8， 12 h after last intragastric administration of tacrolimus. The concentration of tacrolimus in rat whole blood was determined by LC-MS/MS. DAS 2.0 software was used for pharmacokinetic study. RESULTS： Compared with group one， the pharmacokinetic parameters AUC0-12 h， AUC0-∞ and MRT0-12 h of tacrolimus in rats were decreased significantly in group three （P＜0.05），while there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group four （P＞0.05）. Compared with group two， AUC0-12 h of tacrolimus was decreased significantly while CLz was increased significantly in group four （P＜0.05）； there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group five （P＞0.05）. CONCLUSIONS： Single and multiple intragastric administration of berberine hydrochloride has a certain effect on the pharmacokinetics of tacrolimus in rats， it shows that there is a downward trend in blood drug concentration and needs to be used with caution.