泮托拉唑对呱氨托美汀的药动学特征影响研究

Effects of pantoprazole on pharmacokinetics of amtolmetin guacil in rats

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(P<0.05)。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。

OBJECTIVE To investigate effects of pantoprazole on pharmacokinetics of amtolmetin guacil（MED-15）in rats by a single oral gavage of MED-15 or MED-15 combined with specific inhibitor pantoprazole of breast cancer resistance protein（BCRP）.METHODS A total of 12 SD rats were randomly divided into two groups to receive single dose of 100 mg·kg-1（ig）MED-15 or 100 mg·kg-1（ig）MED-15 combined with 60 mg·kg-1 of pantoprazole.MED-15 and its metabolites in rat plasma were determined by HPLC.Pharmacokinetic parameters were calculated by DAS2.0software（non-compartment model）.RESULTS Serum drug concentration-time curve of MED-5 and tolectin in combination group was significantly higher than that in single dose group.Compared with single dose group,AUC0-tvalues of tolectin increased by 2.7 times,tmaxand MRT shortened by 28% and 37%,respectively（P〈0.05）.CONCLUSION Pantoprazole can increase absorption of MED-5,and significantly increase bioavailability of tolectin.