Elsevier

Forensic Science International

Volume 243, October 2014, Pages 74-78
Forensic Science International

The influence of the body mass index (BMI) on the volume of distribution of ethanol

https://doi.org/10.1016/j.forsciint.2014.04.036Get rights and content

Abstract

The volume of distribution of ethanol was already established in 1930s by Widmark. However, since then the average body composition has changed considerably. The effect of the body mass index (BMI) on the volume of distribution of ethanol was evaluated in this study. Fifty healthy volunteers (23 men and 27 women), with BMI-values between 16.0 and 36.0 kg/m2, were asked to drink a dose of 0.4 g ethanol per kilogram body weight after an overnight fast. The ethanol content was measured by a fully validated headspace-GC-FID method. The volume of distribution of ethanol varied between 0.40 and 0.68 L/kg for women, and between 0.43 and 0.73 L/kg for men. For both sexes, the volume of distribution decreased with increasing BMI. Regression analysis resulted in the following equations: volume of distribution = 0.8202  0.0090 × BMI for men (r = 0.66), and 0.7772  0.0099 × BMI for women (r = 0.78). Population probability prediction interval limits were also calculated. In view of the current study, fixed values for the volume of distribution of 0.7 L/kg and 0.6 L/kg for men and women, respectively, often applied in legal blood alcohol calculations, are mainly suited to judge underweight or normal weight people, but not obese persons.

Introduction

Ethanol is one of the oldest and most studied molecules [1], [2]. The relationship between a person’s blood alcohol concentration (BAC), his impairment and the amount of alcohol consumed is important in forensic science. Already in 1930s, Widmark established the following relationship between the BAC (expressed in g/kg) and the administered dose [2]:BAC0=doserho×weightwhere BAC0 = extrapolated blood alcohol concentration (g/kg) at time 0 min, dose = amount alcohol (g), weight = body weight (kg), and rho = Widmark factor.

Widmark found a mean value for rho of 0.68 for men (range 0.51–0.86) and 0.55 for women (range 0.47–0.64) [2].

Rearrangement of this equation gives the following formula:rho=doseBAC0×weightwhich is quite similar to the definition of the volume of distribution (VD) of ethanol:VD=doseBAC0×weightwhere VD = volume of distribution of ethanol (L/kg), dose = amount alcohol (g), BAC0 = extrapolated blood alcohol concentration (g/L) at time 0 min, and weight = body weight (kg).

The ratio between the Widmark factor and VD is the density of blood, which is 1.055 kg/L on average [3]. The VD is the theoretical volume that the total amount of administered drug would have to occupy to provide the same concentration as it currently does in blood, and can be calculated by extrapolation of the zero order elimination kinetics to the Y-axis [2], [3] (Fig. 1).

Ethanol distributes into the total body water (TBW) compartment without binding to plasma proteins and solubility in fat and bone is negligible [4]. Hence, the VD for ethanol is significantly influenced by the proportion of fat to lean body mass (LBM) [5], although very frequently fixed values for VD of 0.7 L/kg for men and 0.6 L/kg for women are used in blood–alcohol calculations [5].

An attempt to individualize Widmark’s factor by calculating the TBW based on the gender, age, height and weight was made in 1982 by Watson et al. [6]. The calculations were later fine-tuned by Gabe [7]. Another possibility is to take into account the body mass index (BMI), which is the weight (in kg) divided by the square of the person’s height (in m). Theoretical calculations and hypothetical nomograms based on the BMI have been published [8], [9], although empirical evidence has not been presented.

Jones [4] published the BAC time courses of two individuals (a man with low BMI and a women with high BMI) after the intravenous administration of 0.4 g ethanol per kilogram body weight. He stressed the need to investigate the VD over a wide range of BMI values given that the average body composition has changed considerably since 1930s with obesity becoming a major health problem.

This study presents the alcohol pharmacokinetics in 50 volunteers, both men and women, evenly distributed over 5 BMI classes, ranging from BMI 16 to 36. The VD of ethanol for each person is calculated, and the influence of the BMI on the VD is evaluated.

Section snippets

Volunteers

This study was approved by the Institutional Review Board of the Ethics Committee of Ziekenhuis Netwerk Antwerpen, Belgium (E.C. Approval N° 3755). Fifty healthy volunteers, both men and women, with BMIs varying between 16.0 and 36.0, were selected from a large database of SGS Life Science Services (Antwerp, Belgium). The study protocol was explained and exclusion criteria (younger than 18 years, pregnancy, renal or hepatic failure, history of alcohol abuse, consumption of more than 21 drinks

Volunteers

The study group consisted of 23 Caucasian men and 27 Caucasian women, divided over 5 BMI-classes: class 1, BMI 16.0–19.9; class 2, BMI 20.0–23.9; class 3, BMI 24.0–27.9; class 4: BMI 28.0–31.9; class 5: BMI 32.0–35.9. Their descriptive statistics are summarized in Table 1 and full details can be found in Supplementary File 1. None of the female volunteers tested positive on the pregnancy test.

Predose BAC and glycemia

Alcohol was not detected in any of the predose samples (limit of detection: 0.015 g/L). Glycemia was

Volunteers

The volunteers were weighed twice: One time at the intake session to select a homogeneous weight distribution, and a second time approximately 30 min before the intake of alcohol. In this way, the dose could be perfectly titrated to 0.4 g/kg body weight. Small differences in weight between the intake session and the day of the experiment occurred, but this did not lead to major imbalances in BMI class distribution (one woman shifted from BMI class 3 to class 2 because of a BMI of 23.8 at the day

Conclusions

To the best of our knowledge, this is the first experimental study that evaluated directly the influence of the BMI on the volume of distribution of ethanol. Although there is a wide variability between subjects with similar BMI, an inverse relationship between volume of distribution and BMI can be established. Many legal blood alcohol concentration calculations use a fixed volume of distribution of 0.7 L/kg for men, and 0.6 L/kg for women, respectively. In view of the current study, these values

Acknowledgements

The authors acknowledge Erik Fransen from the facility for Statistics of the University of Antwerp for his help in constructing the population prediction intervals, Prof. Willy Lambert from Ghent University for his feedback on the example and the staff of SGS Life Science Services in Antwerp (especially Marieke Devos).

References (13)

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This paper is part of the special issue entitled “The 51st Annual Meeting of the International Association of Forensic Toxicologists (TIAFT)”. September 2–3, 2013, Funchal, Medeira, Portugal. Guest edited by Professor Helena Teixeira, Professor Duarte Nuno Vieira and Professor Francisco Corte Real.

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