GASTRIC ORIGIN OF THE 1ST-PASS METABOLISM OF ETHANOL IN HUMANS - EFFECT OF GASTRECTOMY
GASTRIC ORIGIN OF THE 1ST-PASS METABOLISM OF ETHANOL IN HUMANS - EFFECT OF GASTRECTOMY
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DOI：
10.1016/0016-5085(89)91691-0
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发表时间：
1989-11-01
期刊：
影响因子：
29.4
通讯作者：
LIEBER, CS
中科院分区：
文献类型：
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作者：
CABALLERIA, J;FREZZA, M;LIEBER, CS
口服小剂量乙醇后，血液乙醇浓度的曲线下面积（AUC）远小于静脉给药后的AUC。为了研究这种差异是否是由于乙醇在胃、小肠或首次通过肝脏时的氧化所致，我们比较了5名戒酒者通过静脉、口服和十二指肠内途径随机给予相同剂量乙醇后的AUC，以及10名Billroth II胃大部切除术受试者通过前两种途径给予相同剂量乙醇后的AUC。在未手术的受试者中，口服乙醇剂量（0.15 g/kg）后的AUC为静脉给药后AUC的17%（p < 0.01），尽管在AUC完成时> 99%的剂量已从胃中消失。相比之下，十二指肠内给药后的AUC与静脉内给药后的AUC无差异，表明肠道和肝脏对首过代谢均无可检测的贡献。此外，胃切除术完全消除了乙醇的首过代谢。胃代谢降低摄入酒精的生物利用度，从而减轻其全身毒性。在胃切除患者中，这种“保护屏障”的废除可能会增加他们对乙醇的脆弱性。
The areas under the curve (AUCs) of blood ethanol concentrations are much smaller after oral than after intravenous administration of a small dose of ethanol. To study whether this difference is due to ethanol oxidation in the stomach, in the small intestine, or during first pass through the liver, we compared the AUCs after random administration of the same ethanol dose by the intravenous, oral, and intraduodenal routes to 5 abstaining alcoholics and via the two former routes to 10 subjects with Billroth II subtotal gastrectomy. In the nonoperated subjects, the AUCs after an ethanol dose (0.15 g/kg) given orally were 17% (p < 0.01) of those achieved intravenously, in spite of the fact that > 99% of the dose had disappeared from the stomach at the completion of the AUC. By contrast, the AUCs after intraduodenal administration did not differ from those produced intravenously, indicating that neither the intestine nor the liver make a detectable contribution to this first-pass metabolism. Moreover, gastrectomy completely abolished the first-pass metabolism of ethanol. Gastric metabolism decreases the bioavailability of the ingested alcohol and thus attentuates its systemic toxicity. The abolition of this "protective barrier" in gastrectomized patients may increase their vulnerability to ethanol.