Caballeria J, Baraona E, Rodamilans M, Lieber C S
Section of Liver Disease, Bronx Veterans Administration Medical Center, New York.
Gastroenterology. 1989 Feb;96(2 Pt 1):388-92. doi: 10.1016/0016-5085(89)91562-x.
Chronic use of cimetidine and alcohol are commonly associated, but studies on their interactions are the subject of controversy. To investigate this question, a small ethanol dose (0.15 g/kg body wt) was randomly administered on 2 consecutive days either orally or intravenously to 6 normal volunteers, before and after 1 wk of oral administration of 400 mg of cimetidine twice daily. Although cimetidine did not change the areas under the curve of blood ethanol concentrations after intravenous administration, those after oral alcohol intake were twice as large with cimetidine than without. Similar effects were reproduced in rats after intravenous administration of cimetidine (50 mg/kg body wt). In vitro, cimetidine was a noncompetitive inhibitor of gastric alcohol dehydrogenase activity at concentrations as low as 0.01 mM, 100-fold lower than those needed to inhibit the hepatic dehydrogenase. These results indicate that gastric alcohol dehydrogenase activity governs, in part, the systemic bioavailability of ethanol. Consequently, systemic effects of alcohol may be exacerbated in patients receiving cimetidine.
西咪替丁与酒精的长期使用通常有关联，但关于它们相互作用的研究存在争议。为了探究这个问题，在6名正常志愿者口服400毫克西咪替丁，每日两次，持续1周前后，连续两天给他们随机口服或静脉注射小剂量乙醇（0.15克/千克体重）。尽管西咪替丁未改变静脉注射后血液乙醇浓度曲线下面积，但口服酒精后，服用西咪替丁者的曲线下面积是未服用者的两倍。给大鼠静脉注射西咪替丁（50毫克/千克体重）后也出现了类似效果。在体外，西咪替丁在低至0.01毫摩尔的浓度下就是胃乙醇脱氢酶活性的非竞争性抑制剂，该浓度比抑制肝脱氢酶所需浓度低100倍。这些结果表明，胃乙醇脱氢酶活性部分决定了乙醇的全身生物利用度。因此，接受西咪替丁治疗的患者中，酒精的全身效应可能会加剧。
