Mitchell M C, Mezey E, Maddrey W C
Hepatology. 1981 Jul-Aug;1(4):336-40. doi: 10.1002/hep.1840010410.
The effect of chronic ethanol consumption and variations in dietary protein content on microsomal drug metabolism were studied in rats pair-fed liquid diets containing 10, 20, ro 30% dietary protein with or without ethanol. In vitro drug metabolism was measured by aminopyrine breath tests and aminopyrine blood elimination kinetics. In vitro drug metabolism was assessed by measuring aminopyrine N-demethylase activity in the hepatic microsomal fraction. The rate of elimination of aminopyrine in vivo was increased in all ethanol-fed animals (p less than 0.05) regardless of the protein content of the diet. Animals receiving 10 or 20% protein diets with ethanol showed a 36% increase in drug elimination over pair-fed controls as compared to a 17% increase in drug elimination over controls in animals receiving 30% protein diets. Microsomal aminopyrine N-demethylase activities were similar in ethanol/fed animals and pair-fed controls. Cytochrome P-450 content was increased in all ethanol-fed animals (p less than 0.05) but the increase was not dependent on dietary protein content. These results indicate that the effect of chronic ethanol feeding in enhancing drug metabolism in vivo is influenced by the dietary protein content.
研究了长期摄入乙醇以及膳食蛋白质含量变化对微粒体药物代谢的影响，实验采用配对喂养的大鼠，给予含10%、20%或30%膳食蛋白质且添加或不添加乙醇的流质饮食。通过氨基比林呼气试验和氨基比林血液消除动力学来测定体外药物代谢。通过测量肝微粒体部分的氨基比林N-脱甲基酶活性来评估体外药物代谢。无论饮食中的蛋白质含量如何，所有摄入乙醇的动物体内氨基比林的消除率均升高（p<0.05）。与摄入30%蛋白质饮食的动物相比，摄入含10%或20%蛋白质饮食并同时摄入乙醇的动物，其药物消除率比配对喂养的对照组高36%，而摄入30%蛋白质饮食的动物药物消除率比对照组高17%。微粒体氨基比林N-脱甲基酶活性在摄入乙醇的动物和配对喂养的对照组中相似。所有摄入乙醇的动物细胞色素P-450含量均升高（p<0.05），但这种升高并不依赖于膳食蛋白质含量。这些结果表明，长期摄入乙醇对体内药物代谢增强作用受膳食蛋白质含量的影响。
