Evidence based survey of the distribution volume of ethanol: Comparison of empirically determined values with anthropometric measures

Maskell, Peter; Jones, Alan Wayne; Savage, Anne; Scott-Ham, Michael

doi:10.1016/j.forsciint.2018.10.033

Cited by 14 publications

(15 citation statements)

References 24 publications

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“…For a water soluble drug like ethanol, its distribution volume ( V d ) is influenced by a person's age and gender, with lower values observed in women and in elderly men. Table makes a comparison of ethanol V d determined for healthy male and female subjects in controlled drinking experiments (Maskell et al, ). The average V d was 0.69 L/kg for men compared with 0.60 L/kg for women, which suggests that after drinking the same dose/kg of ethanol females achieve a roughly 15% higher peak BAC than males.…”

Section: Absorptionmentioning

confidence: 99%

“…The Widmark‐rho‐factor and the person's BMI are negatively correlated as shown in a drinking study in people with widely different BMI (Maudens et al, ). A recent evidence‐based survey of the distribution volumes of ethanol reported average values of 0.69 L/kg for men and 0.60 L/kg for women as shown in Table (Maskell et al, ). In any individual case, the rho‐factor might vary by a factor of two in the population of drinkers.…”

Section: Pharmacokinetic Calculationsmentioning

confidence: 99%

“…T A B L E 3 The mean and range of ethanol distribution volumes (Widmark rho-factors) for healthy men and women derived from controlled drinking experiments (Maskell, Jones, Savage, & Scott-Ham, 2019 The K m of the class I isozymes of ADH is only 5-10 mg% for ethanol as substrate, which means that it is saturated at all BAC >15-20 mg% (2 × k m ), hence zero-order kinetics. Another form of the ADH enzyme (class IV) is located in the gastric mucosa and is thought to contribute to first-pass metabolism (FPM) of ethanol causing a reduced bioavailability of the dose (Parlesak, Billinger, Bode, & Bode, 2002).…”

Section: Metabolismmentioning

confidence: 99%

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Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations

Jones

2019

WIREs Forensic Science

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The ethanol contained in alcoholic beverages is rapidly absorbed from the gastrointestinal tract and the maximum blood‐alcohol concentration (BAC) is usually reached between 10 and 60 min postdosing. Once in the bloodstream, ethanol is distributed into the total body water (TBW) compartment, which comprises ~55–60% of body weight in nonobese males and ~50–55% in females. The volume of distribution (V d) of ethanol depends on a person's age, gender, and degree of adiposity (ratio of fat to lean tissue). Studies have shown that the average V d for healthy men and women are ~0.70 and ~0.60 L/kg, respectively. Elimination of ethanol from the body occurs primarily through metabolism (92–98% of dose) by hepatic alcohol dehydrogenase (ADH), an enzyme located in the liver cytosol and a microsomal enzyme, denoted CYP2E1. A small fraction (0.1–0.2%) of the dose of ethanol ingested undergoes nonoxidative metabolism by phase II conjugation reactions leading to formation of ethyl glucuronide and ethyl sulfate. Only between 2 and 10% of the dose of ethanol is excreted unchanged in urine, breath, and in sweat/perspiration. Ethanol exhibits dose‐dependent pharmacokinetics, because the hepatic ADH enzyme is saturated with substrate at BAC above 15–20 mg/100 mL (15–20 mg%). Zero‐order kinetics operate for most of the postabsorptive elimination phase and the BAC decreases at a constant rate per unit time ranging from 10 to 35 mg% per hour (average 15 mg% per hour for moderate drinkers). Examples of various pharmacokinetic calculations are presented because these are often necessary in forensic science and legal medicine casework. This article is categorized under: Toxicology > Alcohol Toxicology > Analytical Toxicology Toxicology > Drug‐Impaired Driving

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Section: Absorptionmentioning

confidence: 99%

Section: Pharmacokinetic Calculationsmentioning

confidence: 99%

Section: Metabolismmentioning

confidence: 99%

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Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations

Jones

2019

WIREs Forensic Science

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“…This will give a better estimate of V d than the average (mean) V d across a population (from where previous estimates of the uncertainty of V d were taken). Recent work has demonstrated that the most accurate equations to estimate the V d of an individual are that of Watson, Watson, and Batt for males and Forrest for females (13).…”

Section: Figmentioning

confidence: 99%

The Contribution of Body Mass and Volume of Distribution to the Estimated Uncertainty Associated with the Widmark Equation

Maskell

Cooper

2020

Journal of Forensic Sciences

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The Widmark equation is used forensically for the determination of the amount of ethanol (alcohol) that may have been consumed and also to determine the blood alcohol concentration (BAC) of an individual at a specific time. It is important to be able to estimate the uncertainty associated with Widmark equations. To date, there has been no detailed determination of contribution to the final uncertainty of Widmark calculations of the volume of distribution of ethanol (Vd), using anthropometric equations, or the contribution of an individual’s body mass. Using published data, published literature, and freedom of information data, we determined that the variability (%CV) associated with Vd was ~10% (Watson et al. and Forrest anthropometric equations) and that the %CV associated with estimated body mass was ~15% compared to ~3% when body mass was directly measured. These data allow an estimation of the overall uncertainty of Widmark calculations using general error propagation. The estimated total uncertainty for BAC calculations increased from ~11% (volume consumed) and ~22% (BAC) to ~19% (volume consumed) and ~37% (BAC) when using measured body mass compared to estimated body mass. These results demonstrate that forensic practitioners should be mindful of the increase in estimated uncertainty in calculated Widmark equation results when estimated body mass is used rather than measured body mass. These data further improve the knowledge around the uncertainty of results calculated with the Widmark equation.

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“…Gender‐related difference in body composition mean that after drinking the same dose of ethanol per kg body weight, a woman's BAC is 10–15% higher and thus a correspondingly greater effect on impairment. The higher BAC in women is accounted for by their smaller volume of distribution for ethanol, being on average 0.60 L/kg compared with 0.70 L/kg in males (Maskell, Jones, Savage, & Scott‐Ham, ).…”

Section: Alcoholic Beveragesmentioning

confidence: 99%

Alcohol, its analysis in blood and breath for forensic purposes, impairment effects, and acute toxicity

Jones

2019

WIREs Forensic Science

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Alcohol (ethanol) is man's favorite recreational drug and the psychoactive substance most often encountered in forensic toxicology casework; impaired driving cases, sexual assaults, and drug intoxication deaths. Because of the legal consequences of a person's blood-or breath-alcohol concentration (BAC or BrAC), the analytical methods used must be accurate, precise, and fit for purpose. The gold standard method for determination of ethanol in blood and other biological specimens is gas-liquid chromatography with flame ionization detector, although some laboratories also use a mass spectrometric detector. Also widely used for legal purposes are breath-alcohol analyzers; at the roadside as screening tests and also as evidence for prosecution of traffic offenders. Evidential instruments determine ethanol in exhaled breath by infrared spectrometry at wavelengths of 3.4 and/or 9.5 μm or by electrochemical oxidation with a fuel-cell detector. The impairment of body functions after drinking alcohol depend on the amount consumed (the dose), the speed of drinking and the BAC reaching the brain. After drinking 1-2 units of alcohol (~16 g ethanol) people become more talkative and feel less inhibited (BAC <50 mg%). Cognitive and psychomotor functions are impaired as BAC reaches 80 mg% and at 150 mg% the signs and symptoms of alcohol intoxication are much more obvious including slurred speech, lack of coordination, confusion, and combativeness. On reaching BACs of 300-400 mg% most people are incapacitated and/or unconscious with slow and shallow breathing and at risk of death from paralysis of respiratory centers in the brain stem.

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Evidence based survey of the distribution volume of ethanol: Comparison of empirically determined values with anthropometric measures

Cited by 14 publications

References 24 publications

Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations

Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations

The Contribution of Body Mass and Volume of Distribution to the Estimated Uncertainty Associated with the Widmark Equation

Alcohol, its analysis in blood and breath for forensic purposes, impairment effects, and acute toxicity

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