Matsumoto H, Fukui Y
Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan.
Alcohol Clin Exp Res. 1996 Feb;20(1 Suppl):7A-11A. doi: 10.1111/j.1530-0277.1996.tb01718.x.
The saturation mechanism of hepatic ethanol (EtOH) elimination was studied in the perfused rat liver. EtOH outflow profiles after the instantaneous administration of 3 (mg/ml) x 0.4(ml), 12 x 0.1, 24 x 0.1, and 3 x 0.1 mg (as a dose concentration x a volume) through the portal vein were analyzed by the statistical moment analysis and mathematical models (i.e., dispersion models). Results for 3 x 0.1 and 12 x 0.1 mg doses by moment analysis were similar. This demonstrated that the elimination exhibits linear kinetics. Recovery ratio and hepatic volume of distribution for 3 x 0.4 and 24 x 0.1 mg were larger than those for 3 x 0.1 and 12 x 0.1 mg doses and were similar. Kinetics after administration of 3 x 0.4 and 24 x 0.1 mg may be nonlinear. A difference in the relative dispersion (CV2) obtained by moment analysis between 3 x 0.4 and 24 x 0.1 mg doses indicated different properties of the nonlinear elimination kinetics. There were no differences in all the parameters in the one-compartment dispersion model between 3 x 0.4 and 24 x 0.1 mg doses. In the two-compartment dispersion model, there were differences in the blood volume (VB) and the forward partition rate constant (k12) between 3 x 0.4 and 24 x 0.1 mg (p < 0.05), whereas the elimination rate constant (k sigma) and the dispersion number values for these doses were similar. These findings demonstrated that there is difference in the no-equilibrium process between 3 x 0.4 and 24 x 0.1 mg doses. Therefore, we suggest that the continuous EtOH input into the liver causes the saturation of enzyme pathways and the change of the nonequilibrium process.
在灌注大鼠肝脏中研究了肝脏乙醇（EtOH）消除的饱和机制。通过门静脉瞬间给予3（mg/ml）×0.4（ml）、12×0.1、24×0.1和3×0.1mg（作为剂量浓度×体积）后，用统计矩分析法和数学模型（即扩散模型）分析乙醇流出曲线。3×0.1和12×0.1mg剂量经矩分析法得到的结果相似。这表明消除呈现线性动力学。3×0.4和24×0.1mg剂量的回收率和肝脏分布体积大于3×0.1和12×0.1mg剂量，且二者相似。给予3×0.4和24×0.1mg后的动力学可能是非线性的。3×0.4和24×0.1mg剂量经矩分析法得到的相对扩散（CV2）差异表明非线性消除动力学具有不同特性。3×0.4和24×0.1mg剂量在单室扩散模型中的所有参数均无差异。在双室扩散模型中，3×0.4和24×0.1mg剂量之间的血容量（VB）和前向分配速率常数（k12）存在差异（p<0.05），而这些剂量的消除速率常数（kσ）和扩散数值相似。这些发现表明3×0.4和24×0.1mg剂量之间的非平衡过程存在差异。因此，我们认为持续向肝脏输入乙醇会导致酶途径饱和以及非平衡过程的改变。
