摘要
目的:研究伊马替尼与烯丙基氨基格尔德霉素(17-AAG)联合应用在大鼠体内的药动学,评价药物间的相互作用及联合用药的合理性。方法:用同一剂量组,两种用药方案分别单次给药,用药方案:伊马替尼40 mg.kg-1,伊马替尼40 mg.kg-1加17-AAG15 mg.kg-1。测定大鼠灌胃给药后伊马替尼的血药浓度,采用HPLC法测定大鼠血药浓度,用3p87软件估算药动学参数,SPSS软件进行参数比较。结果:大鼠灌胃给药后伊马替尼的药动学规律可用一室模型来描述。伊马替尼单用及伊马替尼与17-AAG联用的主要药动学参数t1/2、Cmax、tmax、AUC经t检验,均有显著性差异(P<0.05)。结论:伊马替尼与17-AAG联合应用后其药动学特征发生改变,两组分有药动学的相互作用。
OBJECTIVE To evaluate the drug interaction and the rationality of combined drug treatment, the pharmacokinetics of 17-AAG with combinated imatinib in rats were studied. METHODS There are two dosage regimens to administrate in rats separately as follow.imatinib administered at a dose of 40 mg. kg^-1 ;imatinib 40 mg-kg^-1 and 17-AAG 15 mg. kg-1 ;the concentrations of imatinib in rats were determined after intr-agastric (ig) administration. The plasma concentration of the imatinib was measured by reversed phase HPLC, the compartment model was calculated by 3p87 software and the pharmacokinetic parameters were compared with SPSS software. RESULTS Imatinib could be fitted to one compartment model in rats. After intra-gastric administration of imatinib alone or the combination of imatinib with 17-AGG, the main pharmacokinetic parameters t1/2 ,Cmax ,t AUC had significant difference respectively by analysis of test (P〈0. 05). CONCLUSION The pharmacokinetic characters was changed after combined-use of imatinib and 17-AGG, they interacted with each other in pharmacokinetics. There is a drug interaction on each other in rats
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2011年第21期1759-1762,共4页
Chinese Journal of Hospital Pharmacy
基金
贵州省科学技术基金资助项目[编号:黔科合J字(2009)2142号]