Concentration Dependence of Ethanol Metabolism In Vivo in Rats and Man

Abstract

The metabolism of ethanol to acetaldehyde has been widely considered to be almost independent of concentration (i.e., “pseudolinear”) except when blood ethanol was near the Km (0.5–1.0 m/M) of alcohol dehydrogenase (ADH). On the contrary, we report the concentration dependency of ethanol metabolism, in rats and man, at blood ethanol levels several fold the Km of ADH. After intravenous loading, blood ethanol disappearance in 10 rats at blood levels between 38 and 17 m/M ethanol exceeded that between 17 and 4 m/M (14.09 ± 1.38 versus 8.80 ± 0.86 mmoles/liter blood water/hr ± SEM;p < 0.001). Similarly, in 12 men, blood ethanol disappeared faster at 30–17 m/M ethanol compared to 17–4 m/M (5.96 ± 0.33 versus 4.96 7plusmn; 0.28 mmole/liter blood water/hr ± SEM; p < 0.001). When ethanol was maintained at either the 30–60 m/M or 3–19 m/M ethanol range in the blood of 14 fasted rats by constant intravenous infusion, ethanol oxidation was 25% greater at the higher concentration (9.08 ± 0.50 versus 7.23 ± 0.41 mmole/liter blood water/hr ± SEM;p < 0.02). Faster ethanol oxidation at high ethanol concentration could be due to the presence of the microsomal ethanol‐oxidizing system (MEOS), which would only be fully engaged, because of its Km (8.5 m/M), at ethanol levels exceeding those necessary to saturate ADH. The concentration dependency of ethanol metabolism casts doubt on the validity of the common medicolegal practice of calculating prior blood ethanol levels by linear extrapolation of subsequent ones, on the false assumption that metabolism is unaffected by concentration.