Do ethanol and deuterium oxide distribute into the same water space in healthy volunteers?

BACKGROUND The volume of distribution at steady state for ethanol (Vss) is thought to be identical to the total body water (TBW). We compared a two-compartment pharmacokinetic model with parallel Michaelis-Menten and first-order renal elimination with the classical one-compartment zero-order elimination model. Ethanol concentration-time profiles were established for breath, venous blood, and urine. The values of Vss obtained for ethanol were compared with TBW determined by deuterium oxide dilution. METHODS Sixteen healthy volunteers each received a 30-min intravenous infusion of ethanol on two occasions. Ethanol was measured in breath by a quantitative infrared analyzer and in blood and urine by headspace gas chromatography. Deuterium oxide was given as an intravenous injection and measured in serum by isotope-ratio mass spectrometry. Components of variation were calculated by ANOVA to determine the precision of the estimates of Vss and TBW. RESULTS Mean TBW, determined by deuterium oxide dilution, was 44.1 +/- 3.9 liters (+/-SD) for men, corresponding to 0.61 liters/kg, and 37.4 +/- 3.2 liters for women, or 0.54 liters/kg. Estimates of Vss from blood-ethanol pharmacokinetics were 87.6% of TBW according to isotope dilution and 84.4% for breath analysis with the two-compartment model. This compares with 95.1% and 95.4% for blood and breath alcohol, respectively, when the classical zero-order kinetic analysis is used. The precision of the estimates of Vss and TBW was between +/-1.56 and +/-2.19 liters (95% confidence interval). CONCLUSIONS Ethanol does not distribute uniformly into the TBW. The precision of measuring Vss by ethanol dilution was comparable to estimates of TBW by isotope dilution. Results of noninvasive breath ethanol analysis compared well with use of venous blood for estimating Vss. The sophisticated two-compartment model was much superior to the classical one-compartment model in explaining the total concentration-time course of intravenously given ethanol.

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