In Vivo and In Vitro Fates of 8-Hydroxyquinoline Derivatives in Rat

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The in vivo and in vitro fates of 8-hydroxyquinoline (8-OH), 5-chloro-8-hydroxyquinoline (MC), 5,7-dichloro-8-hydroxyquinoline (DC), and 5-chloro-8-hydroxy-7-iodoquinoline (CF) in rat was studied. The results obtained were as follows. (1) These compounds were metabolized to glucuronides and sulfates after intravenous administration. Glucuronides were excreted in bile and urine, but sulfates were excreted exclusively in urine. Unmetabolized forms were almost not excreted. (2) Glucuronides were more excreted in bile as the molecular weights increased by halogen substituents. And glucuronides having the higher affinities to plasma protein and 15% liver 100000 g supernatant fraction were more excreted in bile. (3) Although sulfates were well hydrolyzed as glucuronides in the body, sulfates (especially, CF sulfate) resisted enzymatic hydrolysis in vitro by mitochondria-lysosomal and microsomal enzymes in both liver and kidney in contrast to susceptibilities of glucuronides to them. (4) The conjugates were hydrolyzed by Cu^<2+>, Fe^<3+>, Zn^<2+>, and Mg^<2+>. Especially in the presence of Cu^<2+> or Fe^<3+>, DC sulfate and CF sulfate which were extremely stable in thh enzymatic hydrolysis were unstable. Accordingly, the effects of the metal ions as well as the hydrolytic enzymes were suggested for the hydrolysis of the conjugates in the body.
公益社団法人日本薬学会の論文
1978-05-25