泮托拉唑对呱氨托美汀的药动学特征影响研究

发布时间：2018-09-03 14:03

【摘要】：目的:通过乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)特异性抑制剂泮托拉唑与呱氨托美汀(MED-15)联合用药,考察其对MED-15在大鼠体内药动学的影响。方法:12只SD大鼠随机分为MED-15单独给药组和MED-15联合泮托拉唑给药组。MED-15单独给药组大鼠灌胃给予MED-15 100 mg·kg-1,MED-15联合泮托拉唑给药组灌胃给予泮托拉唑(60 mg·kg-1)及MED-15(100 mg·kg-1)。采用HPLC法测定给药后大鼠血浆内MED-15代谢产物托美汀-甘氨酰胺衍生物(MED-5)及托美汀的浓度,应用DAS 2.0软件进行非房室模型拟合及参数计算。结果:SD大鼠联合给予泮托拉唑和MED-15后,体内MED-5与托美汀的血药浓度时间曲线显著升高。与MED-15单独用药组相比,MED-15联合泮托拉唑给药组托美汀的AUC0-t值增加2.7倍,tmax与MRT分别降低28%和37%,差异均具有统计学意义(P0.05)。结论:泮托拉唑能够增加体内MED-15代谢产物MED-5的吸收程度,显著提高托美汀的生物利用度。
[Abstract]:Aim: to investigate the effect of pam Tora zole, a specific inhibitor of breast cancer resistance protein (breast cancer resistance protein,BCRP (breast cancer resistance protein,BCRP), on the pharmacokinetics of MED-15 in rats. Methods Twelve SD rats were randomly divided into MED-15 group and MED-15 combined with pam Tora group. MED-15 group was given MED-15 100 mg kg-1,MED-15 combined with pam Tora Zol intragastric administration with 60 mg kg-1 and MED-15 (100 mg kg-1). HPLC method was used to determine the concentration of the metabolites of MED-15 in plasma of rats after administration. The concentrations of MED-5 and tometine were measured. The non-atrioventricular model fitting and parameter calculation were carried out by DAS 2.0 software. Results the plasma concentration time curves of MED-5 and tometine were significantly increased in rats treated with pam Tora and MED-15. Compared with MED-15 alone group, the AUC0-t value of metometin group increased by 2.7-fold and MRT decreased by 28% and 37%, respectively. The difference was statistically significant (P0.05). Conclusion: pam Tora can increase the absorption of MED-5, the metabolite of MED-15, and increase the bioavailability of tometine.
【作者单位】：华中科技大学同济医学院同济医院药学部;
【基金】：中央高校基本科研业务费资助(编号:2010JC057)
【分类号】：R965

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