摘要
目的:研究P-糖蛋白抑制剂对蝙蝠葛碱肠吸收的影响。方法:采用在体单向肠灌流法进行小肠吸收实验,利用HPLC法测定灌流液中蝙蝠葛碱的浓度,考察不同浓度P-糖蛋白抑制剂环孢素A、醋酸地塞米松和维拉帕米对蝙蝠葛碱肠吸收的影响。结果:与对照组相比,高浓度和中浓度环孢素A对蝙蝠葛碱的Ka、Papp、P%、吸收量和累积吸收量均有显著性影响(P<0.05),而低浓度时上述参数差异无显著性(P>0.05);与对照组相比,高、中、低3个浓度醋酸地塞米松对蝙蝠葛碱的Ka、Papp、P%、吸收量和累积吸收量均有显著性影响(P<0.05);与对照组相比,高浓度维拉帕米对Dau的Ka、Papp、P%、吸收量和累积吸收量均有显著性影响(P<0.05),而中浓度和低浓度时上述参数无显著性差异(P>0.05)。结论:P-糖蛋白抑制剂环孢素A、醋酸地塞米松和维拉帕米对蝙蝠葛碱均有促吸收作用,其作用大小顺序为醋酸地塞米松>环孢素A>维拉帕米;P-糖蛋白对Dau的肠吸收有外排作用,蝙蝠葛碱为P-糖蛋白底物。
OBJECTIVE To investigate the the effect of P gp inhibitors on intestinal absorption of dauricine in rats. METH- ODS In situ single-pass perfusion model was used and the concentrations of dauricine in perfusate were determined by HPLC. The effects of different concentrations of Pgp inhibitors CsA, Dex and Ver on the intestinal absorption of dauricine were stud- ied. RESULTS Compared with control group, when high and middle concentrations of CsA were administrated, the Ka, Papp, P%, absorption amount and accumulate absorption amount of dauricine increased significantly（P〈0. 05）, however there were no significant increase at low concentration for above parameters（P〉0. 05） ; compared with control group, when high, middle and low concentrations of Dex were administrated, the Ka, Papp, P%, absorption amount and accumulate absorption amount of dauricine increased significantly（P〈0. 05）; compared with control group, when high concentration of Ver was administrated, the Ka, Papp, P%, absorption amount and accumulate absorption amount of dauricine increased significantly（P〈0.05）, howev er there were no significant increases at middle and low concentrations for above parameters（P〉0. 05）. CONCLUSION P-gp inhibitors CsA,Dex and Ver all can promote the absorption of dauricine,P gp can promote efflux of dauricine at intestinal ab- sorption site and dauricine is the substrate of P-gp.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第13期1016-1021,共6页
Chinese Journal of Hospital Pharmacy
基金
成都医学院院级科研课题(项目编号:CYZ09-008)
