Levitt M D, Levitt D G, Furne J, DeMaster E G
Veterans Affairs Medical Center, Minneapolis, Minnesota 55417.
Am J Physiol. 1994 Sep;267(3 Pt 1):G452-7. doi: 10.1152/ajpgi.1994.267.3.G452.
Although the liver has far more ethanol-metabolizing capacity than does the stomach, all first-pass metabolism of alcohol is said to occur in the gastric mucosa because hepatic alcohol dehydrogenase is saturated at low peripheral blood alcohol concentrations. We evaluated the ability of the liver to carry out first-pass metabolism in the rat by constructing a model of hepatic handling of ethanol based on the kinetics of ethanol clearance after intraperitoneal injection of alcohol. Because the efficiency of first-pass metabolism is influenced by the rate of delivery of ethanol, the absorption rate of oral alcohol (0.5 g/kg) was determined and applied to the model. The blood ethanol curves predicted by the model for ethanol delivered via the portal vein or via intravenous infusion were virtually identical to the ethanol curves observed in experimental animals with each of these routes of delivery. We conclude that the liver can account for all first-pass metabolism experimentally observed in the rat, and it is not necessary to postulate some extrahepatic site of first-pass metabolism, such as the stomach.
尽管肝脏的乙醇代谢能力远高于胃，但据说酒精的所有首过代谢都发生在胃黏膜中，因为肝醇脱氢酶在外周血酒精浓度较低时就已饱和。我们通过构建一个基于腹腔注射酒精后乙醇清除动力学的肝脏处理乙醇模型，评估了大鼠肝脏进行首过代谢的能力。由于首过代谢的效率受乙醇输送速率的影响，我们测定了口服酒精（0.5 g/kg）的吸收速率并应用于该模型。该模型预测的通过门静脉或静脉输注输送乙醇的血乙醇曲线，与在实验动物中通过这些输送途径观察到的乙醇曲线几乎完全相同。我们得出结论，肝脏可以解释在大鼠实验中观察到的所有首过代谢，没有必要假定存在一些肝外首过代谢部位，如胃。
