Yumiko Ohbora

Metabolism of acetaldehyde by human erythrocytes

Abstract Acetaldehyde metabolism in human erythrocytes was studied using head-space gas chromatographic determination methods, and it was found that acetaldehyde is metabolized in erythrocytes by NAD dependent cytosolic enzyme having an apparent Km value for acetaldehyde approximately 0.7 mM at pH 7.4, and more than 50% of this activity was reduced by 1 μM disulfiram. So, it is suggested that erythrocytes may have an enzyme system similar to the high Km isozyme of the liver aldehyde dehydrogenase.

Individual differences in the kinetics of alcohol absorption and elimination : A human study.

The individual differences in alcohol pharmacokinetics were studied using the one-compartment model with first-order absorption and zero-order elimination kinetics in humans. The blood alcohol concentrations (BACs) were simulated by obtained parameters, absorption rate constant (ka), and climination rate constant (β). The 81 healthy young Japanese volunteers, who had been divided into those without alcohol-induced facial flushing (nonflushers) and those with facial flushing (flushers) according to alcohol patch test results and a questionnaire beforehand, ingested 0.50 g/kg ethanol within 1 minute. Breath alcohol concentrations (BrACs) were measured during absorption and during the elimination period. BACs were obtained based on BrACs. Fifteen percent of subjects exhibited low BAC profile (below 0.4 mg/mL) (first-pass effect [FPE] group), although the majority showed normal BAC profile (normal group). The ka was approximately 5 to 8 (h−1) in the normal group without significant difference between nonflushers and flushers, whereas that in the FPE group was significantly smaller than in the normal group. For the normal group, peak BACs were well simulated by the one-compartment model with first-order absorption and zero-order elimination kinetics. A considerable portion of subjects exhibited FPE. Absorption of alcohol from the intestine plays an important role in alcohol pharmacokinetics in humans.

Pharmacokinetic study of ethanol and its metabolites during ethanol infusion

We examined the effects of blood ethanol level on the disposition of acetaldehyde and acetate. Rabbits were divided into two groups (1 mg/ml and 2 mg/ml groups). An ethanol saline solution was injected intravenously into these rabbits at 1.0 or 2.0 g/kg body weight for 20 min, followed by constant-rate infusion (0.25 g/kg per h). At 4 and 8 h, the infusion rate was increased to 0.5 g/kg per h for 1 h. Blood ethanol, acetaldehyde and acetate concentrations were measured by headspace gas chromatography. We found that blood ethanol concentration reaches a steady state within 2 h. The blood acetaldehyde concentration exhibited a spike-like increase in response to increases in the blood ethanol level, reaching a steady state around 1 h after the increase. The change in concentration was in proportion to blood ethanol concentration, suggesting that acetaldehyde toxicity may increase with ethanol amount. We also found that blood acetate concentration reaches a steady state within 2 h of administration. The acetate level was constant, and its profile was hardly influenced by increases in the blood ethanol level. Approximately one third of ethanol enters the blood as acetate during ethanol infusion. Our results indicate that the kinetic nature of acetaldehyde is different to that of acetate.

Pharmacokinetic study of ethanol and its metabolites in culture cells.

We examined the disposition of ethanol, acetaldehyde and acetate in culture cells. Rat hepatoma-derived cells, H4IIE, were grown in T-shaped flasks to confluence in minimal essential medium supplemented with 5% fetal bovine serum. For the experimental group, the medium in the flask was replaced with a medium containing a 0, 4, 8 or 20 mM ethanol solution. For the control group, cell-free flasks containing media of the same ethanol concentrations were used. The ethanol, acetaldehyde and acetate concentrations in the flask were measured periodically by headspace gas chromatography. We found that the ethanol concentration of the medium decreased in both the control and the experimental groups; however, the rate of ethanol disappearance differed between these two groups, suggesting that ethanol is metabolized in the culture cells, and that its metabolism is saturated at a lower concentration. The acetaldehyde level was usually markedly low. Acetate was produced both with and without ethanol treatment, but the rate of acetate production increased with ethanol treatment, indicating that a certain percentage of acetate leaks into the medium. These findings suggest that ethanol in culture cells behaves in a kinetic fashion in vivo.