Comparison of D2O and ethanol dilutions in total body water measurements in humans

Abstract

Total body water was measured by ethanol dilution and D2O stable isotope dilution in a group of 20 healthy volunteers (5 females and 15 males), predominantly 23- to 31-year-old students. Both indicator substances were given orally with an ethanol burden of 0.8 g/kg body weight and a D2O burden of 0.1 g/kg body weight after 12-h food and fluid restriction. This first direct comparison of total body water (TBW) from ethanol and D2O dilutions revealed the ethanol compartments to be smaller than those of D2O. The quotient of TBW (ethanol)/TBW (D2O) was 97.7%, which is the order of the quotient TBW (H2(18)O)/TBW (D2O) ( = 97%), well known from the literature and taken to represent relatively exactly the value of TBW overestimation (based on H/D exchange for acid protons) following D2O dilution [36]. Thus the value of TBW (ethanol) is almost identical to that of H2(18)O, which provides direct evidence that ethanol is distributed only in the body water.

The calculation of blood ethanol concentrations in males and females

“…Using the equation of Siri [17], body mass and gas-free body volume lead to very exact calculations of total body fat and fat-free mass but densitometric methods as well as rather imprecise skin-fold caliper measurements require additional assumptions for the estimation of the TBW. In contrast, D 2 O stable isotope dilution allows a direct approach to the TBW compartment and is therefore a universally accepted reference substance for TBW [6,18]. One disadvantage of this method is the reduction of the deuterium concentration in body water by H/D exchange with the acidic protons of organic molecules.…”

“…One disadvantage of this method is the reduction of the deuterium concentration in body water by H/D exchange with the acidic protons of organic molecules. Therefore the D 2 O distribution compartment appears larger, corresponding to the actual size of TBW [18]. For this reason, Grüner and Endres performed dilution experiments with orally administered ethanol (0.8 g/kg body weight) [6,18] which were compared with D 2 O dilutions and revealed the ethanol compartments to be 2.3-3% smaller than those of D 2 O.…”

The clinical significance of variations in ethanol toxicokinetics

“…The volume of distribution (Vd) for ethanol most closely follows the distribution of total body water (usually 50-60% lean body weight for adults) [16]. Since women have less total body water per fraction of body weight, the same amount of ethanol consumed by a woman would reasonably result in a higher serum ethanol level than in a man of equal weight [17].…”

“…The beverages in this model are consumed in equal aliquots over the two hours and absorbed at a rate found in the literature [4][5][6]18]. When known values and ranges for the absorption rate constant (k a ), volume of distribution (Vd), maximum elimination rate (Vmax), and the Michaelis-Menton constant (Km) are obtained from the literature, the peak serum ethanol levels and confidence intervals were generated using a Monte Carlo pharmacokinetic simulator (Boomer v 3.3.1) [16][17][18][19][20][21][22]. As opposed to the crude calculations in Table 1, Figure 1 shows a more realistic potential range of ethanol concentrations over time.…”

Toxicology of Specific Substances

“…The molecules of ethanol are unionised at physiological pH (7.3-7.4) and its small molecular size and high solubility in water means that it easily passes through biological membranes by passive diffusion. Ethanol distributes into the total body water space, which represents about 50-60% of a person's body weight, and ethanol can be used as a tracer in dilution experiments to estimate total body water (Endres and Gruner 1994).…”