Rates of ethanol metabolism decrease in sons of alcoholics following a priming dose of ethanol

Abstract

Rapid changes in rates of ethanol metabolism in response to acute ethanol administration have been observed in animals and humans. To examine whether this phenomenon might vary by risk for alcoholism, 23 young men with a positive family history of alcoholism (FHP) were compared to 15 young men without a family history of alcoholism (FHN). Rates of ethanol metabolism were measured in all subjects first after an initial ethanol dose (0.85 g/kg) and then, several hours later, a second dose (0.3 g/kg), and the two rates were compared. The two groups of subjects were similar in their histories of ethanol consumption. FHP subjects demonstrated faster initial rates of ethanol metabolism, 148 ± 36 mg/kg/hr, compared to FHN subjects, 124 ± 18 mg/kg/hr, p=.01. However, FHN subjects increased their rate of metabolism by 10 ± 27 percent compared to a decrease of -15 ± 24 percent in FHP subjects, p =.007. Fifty-two percent of the FHP and none of the FHN subjects exhibited a decline in metabolic rate of 20% or more, p=.0008. Since a significant proportion of FHP subjects exhibited a decrease in the second rate of ethanol metabolism, these preliminary data might help to partly explain why FHP individuals differ in their sensitivity to ethanol and are more likely to develop alcohol dependence.

Variability in Ethanol Biodisposition in Whites Is Modulated by Polymorphisms in the Adh1b and Adh1c Genes

“…Because at moderate doses ethanol follows a zero‐order elimination, the pharmacokinetic model chosen to calculate all parameters was one‐compartment with extravascular administration and zero‐order elimination 4, 16. Rates of ethanol metabolism were calculated based on the linear rate of decrease in breath ethanol concentrations in the elimination phase 17…”