[男性和女性受试者中酒精及其代谢物药代动力学评估的新方法]

[New methods for pharmacokinetic assessment of alcohol and its metabolites in male and female probands].

作者信息

Kohlenberg-Müller K, Bitsch I

出版信息

Blutalkohol. 1989 Nov;26(6):396-404.

Abstract

The pharmacokinetics of ethanol and its metabolites were examined in 10 young healthy women and men after 1-hr intravenous ethanol application of 7.8 mmol/kg body weight. Therefore, a new pharmacokinetic model takes into account Michaelis-Menten-elimination kinetics of ethanol as well as kinetics of acetaldehyde and acetate, which are defined by first order processes. The metabolite-model adequately describes the ethanol and acetate concentration courses. In fact, the observed ethanol concentrations are so close to the model-predicted values, that the metabolite-model allows an evaluation of half-life-times of acetaldehyde and acetate. The analyses of ethanol infusion studies showed, that there are no sex differences in parameters of ethanol elimination: Maximal elimination velocity Vmax was 3.41 +/- 0.61 mmol/l.h in females and 3.98 +/- 0.69 mmol/l.h in males. Michaelis-Menten-constant kM was 1.49 +/- 0.44 mmol/l and 1.69 +/- 0.88 mmol/l, respectively. In the female group, the volume of distribution of ethanol V1 was with 38.4 +/- 5.0 l significant smaller than in males with 50.5 +/- 3.5 l. In conclusion, the new metabolite-model can be used as a basis for the investigation of the entire alcohol metabolism.

摘要

在10名年轻健康女性和男性中，静脉注射7.8 mmol/kg体重的乙醇1小时后，对乙醇及其代谢产物的药代动力学进行了研究。因此，一种新的药代动力学模型考虑了乙醇的米氏消除动力学以及乙醛和乙酸盐的动力学，它们由一级过程定义。代谢物模型充分描述了乙醇和乙酸盐的浓度变化过程。事实上，观察到的乙醇浓度与模型预测值非常接近，以至于代谢物模型能够评估乙醛和乙酸盐的半衰期。乙醇输注研究分析表明，乙醇消除参数不存在性别差异：女性的最大消除速度Vmax为3.41±0.61 mmol/l·h，男性为3.98±0.69 mmol/l·h。米氏常数kM分别为1.49±0.44 mmol/l和1.69±0.88 mmol/l。在女性组中，乙醇的分布容积V1为38.4±5.0 l，明显小于男性的50.5±3.5 l。总之，新的代谢物模型可作为研究整个酒精代谢的基础。