【摘要】 目的研究20（R）-25-OH-PPD和20（S）-25-OH-PPD在大鼠肠道的立体选择性吸收。方法雄性大鼠通过在体肠灌流手术分别给予20（R）-25-OH-PPD或20（S）-25-OH-PPD,收集一定时间内的肠道流出液及胆汁样品。肠道流出液及胆汁经沉淀蛋白处理,采用LC-MS/MS方法测定其中母体化合物和代谢物含量。同时考察外排蛋白抑制剂对20（R）-25-OH-PPD和20（S）-25-OH-PPD肠道吸收率和胆汁外排率的影响。结果大鼠给予20（R）-25-OH-PPD、20（S）-25-OH-PPD差向异构体后,R和S构型间存在明显的立体选择性吸收,R构型吸收率明显低于S构型。外排蛋白抑制剂不影响这2种异构体的吸收情况,且R和S构型在1.67～41.8μmol·L^-1浓度内呈线性吸收方式。结论肠道的外排蛋白可能不参与20（R）-25-OH-PPD和20（S）-25-OH-PPD异构体在肠道的吸收过程,20（R）-25-OH-PPD和20（S）-25-OH-PPD异构体在肠道的立体选择性吸收可能是由于被动扩散速率不同造成的。更多还原

【Abstract】 Objective To study stereoselective absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD in rat intestine.Methods 20（R）-25-OH-PPD and 20（S）-25-OH-PPD were perfused through rat intestine by surgery.Intestinal perfusion liquid and bile were collected during each 0.5 h.The concentrations of the parent compound and its corresponding metabolites in the samples were determined by LC-MS/MS after the samples were prepared by protein precipitation.The effects of inhibitors of efflux transporters on the intestinal absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD were also investigated in the present study.Results Stereoselective absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD was observed in rat.The absorption rate of 20（R）-25-OH-PPD was markedly slower than that of 20（S）-25-OH-PPD.Efflux protein inhibitors did not affect the absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD.Linear absorption was found for 20（R）-25-OH-PPD and 20（S）-25-OH-PPD in the concentration range of 1.67-41.8 μmol·L^-1.Conclusion Intestinal efflux protein might not be involved in the intestinal absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD.Stereoselective absorption of 20（R）-25-OH-PPD and 20（S）-25-OH-PPD isomers seems caused by their different passive diffusion rates in intestinal tract.更多还原