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灌注大鼠肝脏中乙醇首过效应的评估。

Estimation of ethanol first-pass effect in the perfused rat liver.

作者信息

Matsumoto H, Matsubayashi K, Fukui Y

机构信息

Department of Legal Medicine, Kyoto University Faculty of Medicine, Kyoto, Japan.

出版信息

Alcohol Alcohol Suppl. 1994;29(1):9-13.

PMID:9063826
Abstract

Ethanol elimination was studied in the perfused rat liver. Perfusion was carried out in a single-pass fashion with hemoglobin-free Krebs-Ringer bicarbonate solution. A bolus ethanol dose (1.5, 3, 6, 12 mg/ml, 0.1 ml) was administered through portal vein from a sample loop exchanging a sample injector. Ethanol concentration-time curves of outflow were analyzed by statistical moment analysis. There was no significant difference in the normalized area under the curves [AUC/dose (D)] among doses. Mean transit time (MTT), however, was significantly changed. There was no correlation between AUD/D/g liver weight, or MTT, and D/g liver weight. This suggests that hepatic ethanol elimination exhibited a linear kinetics in the range of doses from 0.15 to 1.2 mg. The recovery ratio at all doses except 0.15 mg was similar to a value of 50%. The first-pass effect in the perfused liver calculated from the recovery ratio was estimated to be a mean value of 51.7% at doses of concentrations from 3 to 12 mg/ml. Our findings suggest that the hepatic saturation of ethanol can be reached by the continuous influx of low concentration of ethanol, rather than instantaneous influx with high ethanol levels.

摘要

在灌注大鼠肝脏中研究了乙醇消除情况。采用无血红蛋白的 Krebs-Ringer 碳酸氢盐溶液以单程方式进行灌注。通过与进样器交换样品的样品环从门静脉给予推注乙醇剂量(1.5、3、6、12 mg/ml,0.1 ml)。通过统计矩分析来分析流出液的乙醇浓度 - 时间曲线。各剂量组曲线下归一化面积[AUC/剂量(D)]之间无显著差异。然而,平均通过时间(MTT)有显著变化。AUD/D/g 肝脏重量或 MTT 与 D/g 肝脏重量之间无相关性。这表明在 0.15 至 1.2 mg 的剂量范围内,肝脏乙醇消除呈现线性动力学。除 0.15 mg 外,所有剂量的回收率均相似,约为 50%。根据回收率计算,在 3 至 12 mg/ml 的浓度剂量下,灌注肝脏中的首过效应估计平均值为 51.7%。我们的研究结果表明,通过持续输入低浓度乙醇而非瞬间输入高乙醇水平,可实现肝脏对乙醇的饱和。

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