In vitro metabolism of amiodarone by rabbit and rat liver and small intestine.
In vitro metabolism of amiodarone by rabbit and rat liver and small intestine.
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发表时间：
1986-07
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通讯作者：
R. Young;H. Mehendale
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作者：
R. Young;H. Mehendale
本研究旨在研究胺碘酮（Am）是否在大鼠和家兔的主要器官和组织中代谢。使用Am和兔和大鼠肺、肝、肾和肠的组织匀浆（600 g上清液）进行孵育，发现肝和肠形成去乙基胺碘酮（DEA）。随后的实验使用后线粒体，胞质和微粒体部分的这些组织表明，Am的代谢是最大的微粒体部分。在这两个物种中，肝源性微粒体检测到更大的DEA形成。在兔和大鼠制剂中，肝微粒体介导的DEA产生因蛋白质浓度而改变，其中5 mg蛋白质浓度提供最大的DEA产生。对于兔，肠微粒体的DEA形成在3 mg蛋白质时最大，但对于大鼠，从1 mg至10 mg蛋白质没有显示出显著变化。在体外代谢的Am的兔和大鼠肝微粒体制剂显着减少1 mM胡椒基丁醚，SKF 525-A，正辛胺，和一氧化碳。这些抑制剂对家兔和大鼠肠道微粒体孵育的影响尚不确定。孵育样品的HPLC分析显示Am代谢存在物种差异，除DEA外还检测到三种代谢物，这一点得到了证明。在兔肝微粒体孵育物中检测到未鉴别代谢产物（I、II、III）。在使用兔十二指肠组织微粒体的孵育物中也检测到代谢产物II。在使用大鼠组织的孵育中未发现DEA以外的代谢物。（250字处删节）
The present studies were designed to investigate whether amiodarone (Am) is metabolized in the major organs and tissues of the rat and rabbit. Incubations using Am and tissue homogenates (600 g supernatant) of rabbit and rat lung, liver, kidney, and gut revealed formation of desethylamiodarone (DEA) by the liver and gut. Subsequent experiments using the post-mitochondrial, cytosolic, and microsomal fractions of these tissues indicated that metabolism of Am was greatest in the microsomal fractions. In both species, greater DEA formation was detected for microsomes of hepatic origin. The hepatic microsomal mediated production of DEA was altered by protein concentration in both the rabbit and rat preparations with protein concentrations of 5 mg providing the greatest DEA production. DEA formation by gut microsomes was greatest at 3 mg of protein for the rabbit but exhibited no significant change from 1 mg to 10 mg of protein for the rat. In vitro metabolism of Am by rabbit and rat hepatic microsomal preparations was significantly reduced by 1 mM piperonyl butoxide, SKF 525-A, n-octylamine, and carbon monoxide. Effects of these inhibitors on rabbit and rat gut microsomal incubations were inconclusive. HPLC analysis of incubation samples revealed a species difference in the metabolism of Am as demonstrated by the detection of three metabolites in addition to DEA. The unidentified metabolites (I, II, III) were detected in rabbit hepatic microsomal incubations. Metabolite II was also detected in incubations using rabbit duodenal tissue microsomes. No metabolites other than DEA were found in incubations using rat tissues.(ABSTRACT TRUNCATED AT 250 WORDS)