乙醇的首过代谢受到胃排空速度的显著影响。
First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying.
作者信息
Oneta C M, Simanowski U A, Martinez M, Allali-Hassani A, Parés X, Homann N, Conradt C, Waldherr R, Fiehn W, Coutelle C, Seitz H K
机构信息
Laboratory of Alcohol Research, Liver Disease and Nutrition, Department of Medicine, Salem Medical Center, Heidelberg, Germany.
出版信息
Gut. 1998 Nov;43(5):612-9. doi: 10.1136/gut.43.5.612.
BACKGROUND
Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol.
AIMS
To study the effect of modulation of GE on FPM of ethanol in the stomach and liver.
METHODS
Sixteen volunteers (eight men and eight women) received ethanol (0.225 g/kg body weight) orally and intravenously, and the areas under the ethanol concentration time curves were determined to calculate FPM of ethanol. In seven of these subjects, FPM of ethanol was measured after the intravenous administration of 10 mg metoclopramide (MCP) and 20 mg N-butylscopolamine (NBS) in separate experiments to either accelerate or delay GE. GE was monitored sonographically by integration of the antral area of the stomach every five minutes for 90 minutes after oral ethanol intake. In addition, gastric biopsy specimens were taken to determine ADH activity and phenotype, as well as to evaluate gastric histology. Blood was also drawn for ADH genotyping.
RESULTS
GE time was significantly delayed by the administration of NBS as compared with controls (p<0.0001) and as compared with the administration of MCP (p<0.0001). This was associated with a significantly enhanced FPM of ethanol with NBS compared with MCP (p = 0.0004). A significant correlation was noted between GE time and FPM of ethanol (r = 0.43, p = 0.0407). Gastric ADH activity did not significantly correlate with FPM of ethanol.
CONCLUSION
FPM of ethanol is strikingly modulated by the speed of GE. Delayed GE increases the time of exposure of ethanol to gastric ADH and may therefore increase gastric FPM of ethanol. In addition, hepatic FPM of ethanol may also be enhanced as the result of slower absorption of ethanol from the small intestine. Thus a knowledge of GE time is a major prerequisite for studying FPM of ethanol in humans.
背景
乙醇在胃和肝脏中经历首过代谢（FPM）。乙醇的胃首过代谢主要取决于胃乙醇脱氢酶（ADH）的活性。此外，胃排空（GE）速度可能会调节乙醇的胃和肝首过代谢。
目的
研究调节胃排空对乙醇在胃和肝脏中首过代谢的影响。
方法
16名志愿者（8名男性和8名女性）口服和静脉注射乙醇（0.225 g/kg体重），测定乙醇浓度-时间曲线下面积以计算乙醇的首过代谢。在其中7名受试者中，分别在静脉注射10 mg甲氧氯普胺（MCP）和20 mg丁基东莨菪碱（NBS）以加速或延迟胃排空的单独实验后测量乙醇的首过代谢。口服乙醇后，每隔5分钟通过整合胃窦面积超声监测胃排空90分钟。此外，采集胃活检标本以测定ADH活性和表型，并评估胃组织学。还采集血液进行ADH基因分型。
结果
与对照组相比（p<0.0001）以及与MCP给药相比（p<0.0001），NBS给药使胃排空时间显著延迟。与MCP相比，这与NBS使乙醇的首过代谢显著增强相关（p = 0.0004）。胃排空时间与乙醇的首过代谢之间存在显著相关性（r = 0.43，p = 0.0407）。胃ADH活性与乙醇的首过代谢无显著相关性。
结论
乙醇的首过代谢受到胃排空速度的显著调节。胃排空延迟增加了乙醇与胃ADH接触的时间，因此可能增加乙醇的胃首过代谢。此外，由于乙醇从小肠吸收较慢，乙醇的肝首过代谢也可能增强。因此，了解胃排空时间是研究人类乙醇首过代谢的主要前提。
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