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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Dronedarone: the effect of diet-induced obesity on its metabolism and experimental hyperlipidemia on its metabolism and tissue distribution in the rat
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Dronedarone: the effect of diet-induced obesity on its metabolism and experimental hyperlipidemia on its metabolism and tissue distribution in the rat

机译:DronedArone:饮食诱导肥胖对其代谢和实验性高脂血症对其代谢和组织分布的影响

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摘要

Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague-Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.
机译:在高脂血症或肥胖症中,在高脂血症和Dronedarone代谢中的DronedArone生物分布进行了评估。雄性Sprague-Dawley大鼠用水或各种高脂肪或高碳水化合物饮食给予正常标准的味道14周。还腹膜内达到泊洛沙姆407的非异胰血糖组。制备肝脏和肠微粒体,然后进行Dronedarone对DesbutyldroneDarone的代谢转化。在口服甲醛的生物分布研究在高脂血症和控制常氧化性血症大鼠中进行。 DronedArone在对照大鼠中对DesbutyldroneDarone的代谢与底物抑制一致。然而,在治疗组中,DesbutyldroneDarone的形成不遵循底物抑制;高脂血症和高卡路里饮食在DronedArone代谢型材中产生了显着的变化,并减少了形成速度。 Dronedarone的组织浓度远高于血浆。此外,与诺罗脂血症相比,在高脂血症中,血浆和肺部Dronedarone浓度明显高得多。

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