奥美拉唑对伊马替尼在大鼠体内药动学参数的影响  

Effect of omeprazole on pharmacokinetic parameters of imatinib in rats

作　　者：赵振寰[1] 荆伟丽[1] 王凯[1] 吕志强[1] 徐文[1] ZHAO Zhenhuan;JING Weili;WANG Kai;LYU Zhiqiang;XU Wen(Dept.of Pharmacy,the Affiliated Hospital of Qingdao University,Shandong Qingdao 266003,China)

机构地区：[1]青岛大学附属医院药学部,山东青岛266003

出　　处：《中国药房》2023年第6期678-681,共4页China Pharmacy

基　　金：山东省自然科学基金资助项目(No.ZR2017MH045);山东省医学会治疗药物监测科研基金项目(No.YXH2020ZX042)。

摘　　要：目的探讨奥美拉唑对伊马替尼在大鼠体内药动学参数的影响。方法将大鼠按体质量分为伊马替尼+低、中、高剂量奥美拉唑组和伊马替尼组,每组6只。各组分别按1.8、3.6、7.2 g/kg的剂量灌胃奥美拉唑混悬液或0.5%羧甲基纤维素钠溶液;1 h后,再按10 mg/kg的剂量灌胃伊马替尼混悬液。分别于灌胃前及灌胃后0.5、1、2、2.5、3、4、5、6、8、12、24、36 h时于眼眶取血100μL,以伊马替尼-d3为内标,采用高效液相色谱-串联质谱法测定大鼠血浆中伊马替尼及其代谢产物N-去甲基伊马替尼的浓度;使用DAS 2.0软件计算两种成分的药动学参数并进行比较。结果与伊马替尼组比较,伊马替尼+中剂量奥美拉唑组大鼠血浆中伊马替尼的AUC_(0-∞)、AUMC_(0-∞)和伊马替尼+高剂量奥美拉唑组大鼠血浆中伊马替尼的c_(max)、t_(1/2)、AUC_(0-∞),AUMC_(0-∞)均显著升高或延长(P<0.05)。与伊马替尼组比较,伊马替尼+中剂量奥美拉唑组大鼠血浆中N-去甲基伊马替尼的AUC_(0-∞)、AUMC_(0-∞)和伊马替尼+高剂量奥美拉唑组大鼠血浆中N-去甲基伊马替尼的c_(max)、AUC_(0-∞)均显著降低(P<0.05)。结论奥美拉唑可提高伊马替尼在大鼠体内的血药浓度并降低代谢产物N-去甲基伊马替尼的血药浓度,可能与伊马替尼代谢过程受到抑制有关。OBJECTIVE To investigate the effects of omeprazole on pharmacokinetic parameters of imatinib in rats.METHODS According to body weight,the rats were divided into imatinib+low-dose,medium-dose,and high-dose omeprazole groups,imatinib group,with 6 rats in each group.They were given omeprazole suspension at the doses of 1.8,3.6 and 7.2 g/kg,or 0.5%sodium carboxymethyl cellulose solution intragastrically respectively;one hour later,imatinib suspension was administered by oral gavage at a the dose of 10 mg/kg.Blood sample(100μL)was taken from the orbit before and 0.5,1,2,2.5,3,4,5,6,8,12,24 and 36 hours after intragastric administration of imatinib.Using imatinib-d3 as internal standard,the plasma concentrations of imatinib and its metabolite N-desmethyl imatinib in rat were determined by high performance liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by DAS 2.0 software and compared.RESULTS Compared with imatinib group,AUC_(0-∞)and AUMC_(0-∞)of imatinib in rat plasma of imatinib+medium-dose omeprazole group,cmax,t_(1/2),AUC_(0-∞)and AUMC_(0-∞)of imatinib in rat plasma of imatinib+high-dose omeprazole group were all increased or prolonged significantly(P<0.05).Compared with imatinib group,AUC_(0-∞)and AUMC_(0-∞)of N-desmethyl imatinib in rat plasma of imatinib+medium-dose omeprazole group,and cmax and AUC0→∞of N-desmethyl imatinib in rat plasma of imatinib+high-dose omeprazole group were decreased significantly(P<0.05).CONCLUSIONS Omeprazole may increase the plasma concentration of imatinib in rats and reduce the plasma concentration of N-desmethyl imatinib in rats,which may be associated with inhibiting the metabolism of imatinib.

关 键 词：奥美拉唑 伊马替尼 N-去甲基伊马替尼 药动学 大鼠 

分 类 号：R969.1[医药卫生—药理学] R969.2[医药卫生—药学]