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目的:应用群体药理学方法探讨血浆中乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸(H/A)比值及乳酸/丙酮酸(L/P)比值变化的效应.方法:给14名健康成人口服剂量相当于1.02 g·L-1总身体水的乙醇.在另一项实验中,给8名健康成人静脉注射剂量相当于0.83 g·L-1总身体水的乙醇.在服用乙醇后380 min采取静脉血测定乙醇,β-羟丁酸,乙酰乙酸,乳酸及丙酮酸的血浆浓度.在静注乙醇后340min采血测定上述5种物质的血浆浓度.结果:在口服乙醇实验中,G0为66.6±8.1 mg·dl-1,显著低于102mg·dl-1,(t检验,P＜0.001).清除相斜率β为0.229±0.05 mg·dl-1·min-1.在静注实验中,G0为75.6±10.9 mg·dl-1,与83 mg·dl-1比较无显著性差异,β为0.245±0.05mg·dl-1·min-1.在两项实验中,我们应用群体间接生理反应模型来拟合乙醇浓度对β-羟丁酸,乙酰乙酸,乳酸,丙酮酸,β-羟丁酸/乙酰乙酸比值及乳酸/丙酮酸比值变化的效应,并得出各项参数.同时,我们发现,当乙醇的清除相结束时,H/A比值尚未达最大值,说明在乙醇的零级代谢相时肝脏仍在产生NADH.乳酸和乙醇的关系曲线显示乳酸的变化呈现一种逆时钟方向的滞后.结论:血L/P比值不适合用作实时肝脏氧化状态的指标.本研究提供的参数将有益于将来研究乙醇对肝脏氧化状态的影响.“,”To investigate the relationship between plasma concentration of β-hydroxybutyrate, acetoacetate, lactate, pyruvate, β-hydroxybutyrate/acetoacetate (H/A ratio) and lactate/pyruvate (L/P ratio) and alcohol by population PD analysis after oral or intravenous administration of alcohol. METHODS: An oral dose of alcohol tered to 14 normal human subjects and an Ⅳ infusion (30 water was administered to 8 normal subjects. Venous blood was sampled for determination of alcohol (BAC),β-hydroxybutyrate, acetoacetate, lactate and pyruvate for 380 min after oral administration and for 340 min after Ⅳ administration. RESULTS: After oral administration,The slope β for eliminate-phase was 2.29 ± 0.50 oral or Ⅳ administration, the relationship between BAC and β-hydroxybutyrate, acetoacetate, lactate and pyruvate concentration and H/A and L/P ratio were investigated by population physiologic indirect response model, and the parameters were presented. Meanwhile, the H/A did not reach maximum at the end of the elimination phase of the alcohol, and it suggested that the liver continue to accumulate NADH at zero-orden metabolism phase of alcohol.The plot of BAC versus the plasma concentration of lactate showed an apparent counter-clockwise hysteresis. CONCLUSION: In general, venous blood L/P ratio is not a suitable index for the real time reflection of liver redox status because of the time lag change in concentration of lactate after administration of ethanol. The parameters provided here can be useful for future researches on the effect of alcohol on liver redox status.