Genetic and environmental factors affecting ethanol metabolism in man

Abstract

The relative contribution of genetic and environmental factors to maintaining twofold differences in rates of ethanol elimination from plasma was examined in 14 sets of nonmedicated, nonhospitalized healthy twins. After a single oral dose of 1 ml. per kilogram of 95 per cent ethanol, intrapair differences in rates of elimination were less in identical than in fraternal twins. Thew results indicate that individual differences in rates of ethanol elimination among the 28 twins were genetically controlled and that environmental factors played a negligible role. In 6 prisoners in solitary confinement, rates of ethanol metabolism increased in 3 but declined in the remaining 3 after 21 days of ethanol administration. Rates of antipyrine elimination from pla~ma were accelerated by ethanol administration in each of the 6 volunteers. Considerable individual variation occurred in the degree to which ethanol shortened plasma antipyrine half-lifes; reduction ranged from 4 to 37 per cent of the initial antipyrine half-life. These results suggest that ethanol administration for 21 days at this dosage fails to alter consistently the rate of its own metabolism but increases antipyrine metabolism in all subjects to vary:ng extents.

Monogenic control of variations in antipyrine metabolite formation. New polymorphism of hepatic drug oxidation.

“…Similar family studies should be performed on rate constants for formation of the principal metabolites of amobarbital (5), dicoumarol (6), ethanol (7), halothane (8), phenylbutazone (9), phenytoin (10), and salicylate (11), since twin studies on these drugs indicated that in uninduced subjects genetic factors determined large interindividual variations in the kei of the parent drug. The time is now ripe to perform family studies on the metabolites of these drugs.…”

“…The results reflected not only the design of the particular study but also the criteria used to select subjects (1). The conclusion that genetic factors are primarily responsible for such variations Received for publication 24 September 1982 and in revised form 4 January 1983. among normal subjects under carefully controlled, relatively noninducing environmental conditions derived from studies using antipyrine (AP) (2)(3)(4),' amobarbital (5), dicoumarol (6), ethanol (7), halothane (8), phenylbutazone (9), phenytoin (10), and salicylate (11). Nevertheless, it is also well recognized that numerous other host factors, including many disease states, can alter the genetically controlled capacity of a subject to eliminate certain drugs (1).…”

Ethanol ‘dose‐dependent’ elimination: Michaelis‐Menten v classical kinetic analysis.

“…This view has been perpetuated by many investigators with the use of arithmetic linear regression techniques and Widmark's coefficients (Kopun & Propping, 1977;Newman, Lehman & Cutting, 1937;Vesell, Page & Passananti, 1971). Haggard & Greenberg (1934) first suggested concentrationdependent elimination rates for ethanol and Lundquist & Wolthers (1958) showed that the Michaelis constant derived from experiments in man closely approximated that for alcohol dehydrogenase (ADH) in vitro.…”

Acute toxicity of gasoline and some additives.

“…Flushed face, tachycardia, and nausea were associated with higher blood acetaldehyde levels in this study. Vesell et al (46) examined the effects of genetic and environmental factors on ethanol metabolism in humans. The results indicated that individual differences in rates of ethanol metabolism among 28 twins were genetically controlled and that environmental factors played a negligible role.…”