Kotaki H, Yamamura Y, Tanimura Y, Saitoh Y, Nakagawa F, Tamura Z
J Pharmacobiodyn. 1984 Jun;7(6):420-5. doi: 10.1248/bpb1978.7.420.
The existence of the enterohepatic circulation (EHC) of clioquinol was confirmed by using paired rats, donor and recipient, which were connected to each other with a bile duct-to-duodenum cannula. The concentrations of clioquinol and its metabolites appearing in the plasma of the recipient following intraduodenal 10 mg/kg dose of clioquinol to the donor were fairly low. However, within 24 h after the administration ca. 12% of the dose was reexcreted in the bile of the recipient as clioquinol glucuronide and ca. 2% in the urine as clioquinol sulfate. From these results and the data of biliary excretion in our previous paper, the glucuronide was found to play a role on the EHC. Further, both in vitro and in situ results suggested that clioquinol glucuronide excreted in the bile may be absorbed partially after return to the parent drug in the intestinal tract and partially as such without deconjugation.
通过使用供体和受体配对的大鼠，用胆管-十二指肠插管将它们连接起来，证实了氯碘羟喹的肝肠循环（EHC）的存在。给供体十二指肠内注射10mg/kg剂量的氯碘羟喹后，受体血浆中出现的氯碘羟喹及其代谢物的浓度相当低。然而，给药后24小时内，约12%的剂量以氯碘羟喹葡萄糖醛酸苷的形式重新排泄到受体的胆汁中，约2%以氯碘羟喹硫酸盐的形式排泄到尿液中。根据这些结果以及我们之前论文中的胆汁排泄数据，发现葡萄糖醛酸苷在肝肠循环中起作用。此外，体外和原位结果均表明，排泄到胆汁中的氯碘羟喹葡萄糖醛酸苷在肠道中可能部分还原为母体药物后被吸收，部分则未经去结合直接被吸收。
