Pharmacokinetic study of ethanol and its metabolites during ethanol infusion

Abstract

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.