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Do Ethanol and Deuterium Oxide Distribute Into the Same Water Space in Healthy Volunteers?
Author(s) -
Norberg Åke,
Sandhagen Bo,
Bratteby LarsEric,
Gabrielsson Johan,
Jones Alan Wayne,
Fan Hu,
Hahn Robert G.
Publication year - 2001
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2001.tb02143.x
Subject(s) - chemistry , body water , deuterium , dilution , urine , ethanol , chromatography , pharmacokinetics , liter , alcohol , isotope dilution , mass spectrometry , medicine , biochemistry , body weight , physics , quantum mechanics , thermodynamics
Background: The volume of distribution at steady state for ethanol (V ss ) 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 V ss 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 V ss 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 V ss 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 V ss 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 V ss 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 V ss . 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.