乙醇对ethylmorphine分离大鼠肝细胞代谢:通过multicompartmental模型的描述。

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徐BQ Aasmundstad助教,Lillekjendlie B, Bjorneboe, Christophersen,河J

乙醇对ethylmorphine分离大鼠肝细胞代谢:通过multicompartmental模型的描述。

Toxicol杂志》1997年4月,80 (4):171 - 81。

PubMed ID

9140136 (在PubMed

]

文摘

肝细胞色素p - 450酶调节至少两个重要的生物转化途径可待因和ethylmorphine与去甲基或O-dealkylation开始,随后产生极性代谢物然后glucuronidated。本研究旨在描述急性乙醇对ethylmorphine的新陈代谢的影响和比较它与影响可待因在新鲜分离大鼠肝细胞悬浮液。从雄性Wistar鼠分离大鼠肝细胞是由胶原酶灌注方法。Ethylmorphine,可待因及其代谢物量化通过高效液相色谱法与紫外检测。总ethylmorphine消除速率降低了12%在5毫米和100毫米38%乙醇。相应的百分比为可待因16和43%。乙醇的浓度存在的几种中间和最终产品的ethylmorphine和可待因从控制情况发生了显著的变化。实验数据被应用到一个数学分为若干部分的线性模型估计的影响乙醇在单独的反应速率两个主要代谢途径。ethylmorphine实验中的反应速率常数之间的比率在100和0毫米乙醇ethylmorphine - - > norethylmorphine 0.65, 0.63 norethylmorphine——> normorphine 0.56 ethylmorphine - - >吗啡,吗啡- - > normorphine 0.49, 0.31 normorphine - - > normorphine-3-glucuronide吗啡- - > morphine-3-glucuronide和0.49。近发现了类似的乙醇对可待因代谢的影响。 In additional experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine was found to be inhibited by ethanol in a concentration-dependent manner. The glucuronidation of morphine and normorphine added in separate experiments was also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to 60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100 mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine (and codeine) leading to the end products morphine-3-glucuronide and normorphine-3-glucuronide were inhibited by ethanol, and that the glucuronidation process were the ones most affected by ethanol.

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药物

Ethylmorphine