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WIREs Forensic Sci

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

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Abstract 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
Schematic block diagram depicting the disposition and fate of ethanol in the body, resulting in a BAC profile and impacting on cerebral functions causing impairment
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Concentration‐time profiles of ethanol in blood with samples taken at 5 min intervals from high to low ethanol concentrations. The left plot on Cartesian coordinates shows the hockey stick shape characteristic of drugs with saturation kinetics. The right plot shows a logarithmic transformation of the BAC measurements and existence of zero‐order kinetics (BAC > 20 mg%) and first‐order kinetics (BAC <15–20 mg %)
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Frequency distribution of the rates of ethanol elimination from blood in apprehended drunken drivers in Sweden. These results were derived from the change in BAC between two blood samples taken about 60 min apart. Values under 10 mg% per hour probably reflect those drivers who were not on the post‐peak phase when the first blood sample was taken
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Concentration‐time profile of ethanol in blood for one subject who drank 0.80 g/kg body weight in 30 min after an overnight fast. The method used to derive the β‐slope or zero‐order elimination rate is shown as the gradient of the rectilinear descending phase
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Concentration‐time profiles of ethanol in blood after three doses of ethanol were consumed on an empty stomach in 15–25 min. Average curves are shown for N = 16 subjects ingesting each dose of ethanol. The rectilinear descending phase is marked for each dose of ethanol
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Comparison of the metabolism of ethanol and methanol in the liver by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes into more toxic metabolites, acetaldehyde and formaldehyde. Also shown are the chemical structures of the enzyme inhibitors 4‐methyl pyrazole (ADH) and disulfiram (ALDH)
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The metabolism and excretion of ethanol in the body showing the approximate amount eliminated by oxidative and nonoxidative pathways and in the exhaled breath, urine, and sweat
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Toxicology > Alcohol
Toxicology > Analytical Toxicology
Toxicology > Drug-Impaired Driving

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