乙醇氧化过程中乙酸的米氏消除动力学。

Fujimiya T, Li Y J, Ohbora Y

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

Alcohol Clin Exp Res. 2000 Apr;24(4 Suppl):16S-20S.

BACKGROUND

The redistribution of acetate cannot be explained using a linear kinetic model. We studied the pharmacokinetics of acetate during ethanol oxidation in the rabbit.

METHODS

An ethanol saline solution (0.5, 1.5, and 2.5 g/kg) was injected bolus intravenously. We measured blood ethanol, acetaldehyde, and acetate concentrations by using head-space gas chromatography.

RESULTS

Blood acetate concentration changed in three phases: an ascending, a plateau, and a declining phase. The first-order rate constant of the declining phase was smaller than that of the ascending phase and decreased dose dependently. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve (AUC/Dose) and the mean residence time (MRT) increased with increasing dose amount. These increases suggest a capacity-limited elimination of acetate. We attempted simultaneous multiline fitting, using the three blood acetate disappearance curves, to determine the pharmacokinetic model. Consequently, the blood acetate profile was best described by a Michaelis-Menten elimination kinetic model. The Vmax and Km values of acetate elimination were 40.80 +/- 14.10 mM/hr and 0.47 +/- 0.19 mM, respectively. The fraction of a dose of ethanol converted to acetate (f(AcA)) was calculated to be 0.54. The estimated values are average parameter values of three different doses. Fitted curves suggest smaller f(AcA) at a low dose and larger f(AcA) at a higher dose, which indicate increases of accumulation and redistribution of acetate at higher doses.

CONCLUSIONS

Acetate elimination during ethanol oxidation obeys capacity-limited kinetics.

背景

乙酸盐的再分布无法用线性动力学模型来解释。我们研究了家兔乙醇氧化过程中乙酸盐的药代动力学。

方法

静脉推注乙醇盐溶液（0.5、1.5和2.5 g/kg）。我们采用顶空气相色谱法测量血液中的乙醇、乙醛和乙酸盐浓度。

结果

血液乙酸盐浓度变化呈三个阶段：上升阶段、平台期和下降阶段。下降阶段的一级速率常数小于上升阶段，且呈剂量依赖性降低。对血液乙酸盐曲线进行统计矩分析表明，曲线下归一化面积（AUC/剂量）和平均驻留时间（MRT）随剂量增加而增加。这些增加表明乙酸盐的消除存在容量限制。我们尝试用三条血液乙酸盐消失曲线进行同步多线拟合，以确定药代动力学模型。因此，血液乙酸盐曲线最好用米氏消除动力学模型来描述。乙酸盐消除的Vmax和Km值分别为40.80±14.10 mM/小时和0.47±0.19 mM。计算得出乙醇剂量转化为乙酸盐的分数（f(AcA)）为0.54。这些估计值是三种不同剂量的平均参数值。拟合曲线表明，低剂量时f(AcA)较小，高剂量时f(AcA)较大，这表明高剂量时乙酸盐的积累和再分布增加。