泮托拉唑抑制人乳腺癌耐药蛋白对大鼠体内舍曲林脑分布的影响

Effects of Pantoprazole by inhibiting Bcrp on Sertraline brain distribution in rats

目的采用LC-MS/MS方法测定大鼠血浆及脑中的舍曲林,研究人乳腺癌耐药蛋白(Bcrp)是否介导了舍曲林的跨膜转运及泮托拉唑抑制Bcrp是否会影响舍曲林的脑分布。方法尾静脉单独给予舍曲林及联合给予舍曲林和Bcrp抑制剂泮托拉唑,分别在0.5、1、2、4 h时测定血浆及脑中的舍曲林浓度。结果不加抑制剂的血浆AUC0-4 h显著高于加入抑制剂组,而脑中AUC0-4 h未出现显著性的差异,计算得到的PAN/WT brain(B)/plasma(P)值为1.5,4 h的PAN/WT B/P值为2.4。结论Bcrp可能介导了舍曲林的外排,但不会因此使泮托拉唑对舍曲林的脑分布产生影响。

OBJECTIVE To establish an LC-MS/MS method for the determination of Sertraline in rat plasma and brain,and to study whether Bcrp mediates Sertraline transmembrane transport and whether Bcrp affects Sertraline brain distribution.METHODS Sertraline concentration in plasma and brain was measured at 0.5,1,2 and 4 h after tail vein injection of Sertraline and combined injection of Sertraline and Pantoprazole,a BCRP inhibitor.RESULTS The plasma AUC0-4 h of Sertraline without inhibitor was significantly higher than that with inhibitor,but there was no significant difference in brain AUC0-4 h.The calculated PAN/WT brain(B)/plasma(P)value was 1.5 and PAN/WT B/P value was 2.4 at 4 h.CONCLUSION Bcrp may mediate the efflux of Sertraline,but it does not affect the brain distribution of Sertraline by Pantoprazole.