• Ethanol Metabolism;
  • First-Pass Metabolism;
  • Pharmacokinetics;
  • Alcohol Dehydrogenase

The effect of the concentration of ingested ethanol on the resulting blood alcohol concentrations (BAC) was tested in both humans and rats. In humans, when 0.3 g/kg body weight ethanol was ingested postprandially, the mean area under the blood alcohol curve (AUC) and the mean peak BAC were significantly lower with a concentrated (40% w/v) than with a dilute (4%) solution. Similarly, rats in the fed state exhibited decreasing mean AUCs with increasing concentrations (4%, 16%, and 40%) of intragastrically administered ethanol (1.0 g/kg). Pharmacokinetic analysis comparing intragastric and intraperitoneal administration of ethanol to rats indicated that the more concentrated solution resulted in less alcohol reaching the systemic circulation (4%: 0.896 ± 0.071 g/kg; 16%: 0.772 ± 0.072 g/kg; 40%: 0.453 ± 0.037 g/kg) and suggested that this effect could be attributed to two factors: increased gastric retention of ethanol (4%: 0.109 ± 0.024 g/kg; 16%: 0.102 2 0.016 g/kg; 40%: 0.214 ± 0.042 g/kg) and a large increase in first-pass metabolism (4%: 0.004 ± 0.054 g/kg; 16%: 0.145 ± 0.048 g/kg; 40%: 0.329 ± 0.044 g/kg).

In contrast to the results in the fed state, in humans fasted overnight the concentration of alcohol consumed (4%, 16%, and 40%) had no significant effect on mean AUCs. In fasted rats, mean AUCs after intragastric intubation of the two lower concentrations of ethanol (4% and 16%) were comparable to those found after intraperitoneal injection, and only the highest ethanol concentration (40%) produced a lower mean AUC.

Our results demonstrate that the consumption of a concentrated solution of ethanol results in lower blood alcohol levels than does a dilute solution, when subjects are tested in the fed state. This effect is associated with more first pass metabolism and less bioavailability with the high ethanol concentrations. These findings now raise the issue whether ethanol in low concentration beverages such as beer and wine has a greater bioavailability than in distilled spirits.