Norberg A, Gabrielsson J, Jones A W, Hahn R G
Department of Anaesthesia and Intensive Care, Huddinge University Hospital, Huddinge, Sweden.
Br J Clin Pharmacol. 2000 May;49(5):399-408. doi: 10.1046/j.1365-2125.2000.00194.x.
To evaluate the prerequisites for using ethanol dilution to estimate total body water, we studied the within- and between-subject variation in the parameter estimates of a two-compartment model for ethanol pharmacokinetics with parallel Michaelis-Menten and first-order renal elimination. Because sampling of breath might be preferable in some clinical situations the parameter estimates derived from breath and venous blood were compared.
On two occasions, ethanol 0.4 g kg-1 was given by intravenous infusion to 16 volunteers after they had fasted overnight. The proposed model was fitted by means of nonlinear regression to concentration-time data measured in the breath, venous blood and urine during 360 min. The model contained six parameters: Vmax and Km (Michaelis-Menten elimination constants), CLd (intercompartmental distribution parameter), VC and VT (volumes of the central and tissue compartment, respectively) and CLR (renal clearance). The volume of distribution, Vss, was calculated as the sum of VC and VT.
The mean +/- total s.d. of the parameter estimates derived from blood data were Vmax 95 +/- 25 mg min-1, Km 27 +/- 19 mg l-1, CLd 809 +/- 232 ml min-1, VC 14.5 +/- 4.3 l, VT 21. 2 +/- 4.4 l, CLR 3.6 +/- 2.0 ml min-1 and Vss 35.8 +/- 4.3 l. The variation within subjects amounted to 3%, 9%, 21%, 21%, 17%, 26% and 2%, respectively, of the total variation. Breath samples were associated with a similar or lower variation than blood, both within and between subjects. About 1.5% of the infused ethanol was recovered in the urine.
The low within-subject variation of the key parameter Vss (only 2%) suggests that ethanol dilution analysed by the pharmacokinetic model applied here may be used as an index of the total body water. Breath samples yielded at least as good reproducibility in the model parameters as venous blood.
为评估使用乙醇稀释法估算总体水的前提条件，我们研究了具有平行米氏（Michaelis-Menten）和一级肾清除的乙醇药代动力学二室模型参数估计值的个体内和个体间变异。由于在某些临床情况下采集呼气样本可能更可取，因此对从呼气和静脉血得出的参数估计值进行了比较。
16名志愿者隔夜禁食后，分两次静脉输注0.4 g/kg乙醇。通过非线性回归将所提出的模型拟合到360分钟内呼气、静脉血和尿液中测得的浓度-时间数据。该模型包含六个参数：Vmax和Km（米氏消除常数）、CLd（室间分布参数）、VC和VT（分别为中央室和组织室的容积）以及CLR（肾清除率）。分布容积Vss计算为VC与VT之和。
从血液数据得出的参数估计值的均值±总标准差为：Vmax 95±25 mg/min，Km 27±19 mg/l，CLd 809±232 ml/min，VC 14.5±4.3 l，VT 21.2±4.4 l，CLR 3.6±2.0 ml/min，Vss 35.8±4.3 l。个体内变异分别占总变异的3%、9%、21%、21%、17%、26%和2%。无论是个体内还是个体间，呼气样本的变异与血液相似或更低。约1.5%的输注乙醇在尿液中回收。
关键参数Vss的个体内变异较低（仅2%），表明此处应用的药代动力学模型分析的乙醇稀释法可作为总体水的指标。呼气样本在模型参数方面产生的重现性至少与静脉血一样好。
