摘要
Objective：Salidroside showed potential pharmacological effect on plateau hypoxia and cardiovascular disease like myocardial ischemia.However,pharmacokinetic differences have not been assessed between the pathological model and the normal animals.This study focused on evaluating the pharmacokinetic properties of salidroside in animals with myocardial ischemia.Methods：A reproducible and sensitive method was established and optimized based on liquid chromatography tandem mass spectrometry（LC–MS/MS）to determine salidroside in rats plasma.The data showed thesalidroside proportionally increased along with dose elevation after singly intragastric administration of salidroside at a dose of 20,50,and 100 mg/kg.Results：Compared to the single dose,the Cmax,andsalidroside markedly decreased while CL/F and V/F increased after multiple dosing.However,theischemic model rats were 0.35 and 0.39 fold lower than those in normal rats after a single dose at 50 mg/kg,with an increased CL/F and V/F.Surprisingly,after a consecutive administration of salidroside for 7 d,the mean Cmax,2.89 and 2.61 fold higher than a single dose in model rats,and even 2.28 and4.03 fold higher than the normal controls after multiple doses.All the above fold values were statistically different（P〈0.01）.Conclusion：The particular PK properties of salidroside in ischemic model rats were presented in our study for the first time,suggesting that myocardial ischemia greatly affected pharmacokinetics exposure of the orally administrated salidroside after a single or multiple doses.
Objective：Salidroside showed potential pharmacological effect on plateau hypoxia and cardiovascular disease like myocardial ischemia.However,pharmacokinetic differences have not been assessed between the pathological model and the normal animals.This study focused on evaluating the pharmacokinetic properties of salidroside in animals with myocardial ischemia.Methods：A reproducible and sensitive method was established and optimized based on liquid chromatography tandem mass spectrometry（LC–MS/MS）to determine salidroside in rats plasma.The data showed thesalidroside proportionally increased along with dose elevation after singly intragastric administration of salidroside at a dose of 20,50,and 100 mg/kg.Results：Compared to the single dose,the Cmax,andsalidroside markedly decreased while CL/F and V/F increased after multiple dosing.However,theischemic model rats were 0.35 and 0.39 fold lower than those in normal rats after a single dose at 50 mg/kg,with an increased CL/F and V/F.Surprisingly,after a consecutive administration of salidroside for 7 d,the mean Cmax,2.89 and 2.61 fold higher than a single dose in model rats,and even 2.28 and4.03 fold higher than the normal controls after multiple doses.All the above fold values were statistically different（P〈0.01）.Conclusion：The particular PK properties of salidroside in ischemic model rats were presented in our study for the first time,suggesting that myocardial ischemia greatly affected pharmacokinetics exposure of the orally administrated salidroside after a single or multiple doses.
基金
the National Natural Science Foundation of the People’s Republic of China(81573495,81530098)
the National Key Special Project of Science and Technology for Innovation Drugs of China(2015zx09501001,2017ZX09301013)
the foundation support from Jiangsu Province Natural Science Foundation(BL2014070)
the project of university collaborative innovation center of Jiangsu province(Modern Chinese medicine center and biological medicine center)
