Michaelis-Menten elimination kinetics of acetate during ethanol oxidation

The redistribution of acetate cannot be explained using a linear kinetic model. We studied the pharmacokinetics of acetate during ethanol oxidation in the rabbit.

An ethanol saline solution (0.5, 1.5, and 2.5 g/kg) was injected bolus intravenously. We measured blood ethanol, acetaldehyde, and acetate concentrations by using head-space gas chromatography.

Blood acetate concentration changed in three phases: an ascending, a plateau, and a declining phase. The first-order rate constant of the declining phase was smaller than that of the ascending phase and decreased dose dependently. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve (AUC/Dose) and the mean residence time (MRT) increased with increasing dose amount. These increases suggest a capacity-limited elimination of acetate. We attempted simultaneous multiline fitting, using the three blood acetate disappearance curves, to determine the pharmacokinetic model. Consequently, the blood acetate profile was best described by a Michaelis-Menten elimination kinetic model. The Vmax and Km values of acetate elimination were 40.80 +/- 14.10 mM/hr and 0.47 +/- 0.19 mM, respectively. The fraction of a dose of ethanol converted to acetate (f(AcA)) was calculated to be 0.54. The estimated values are average parameter values of three different doses. Fitted curves suggest smaller f(AcA) at a low dose and larger f(AcA) at a higher dose, which indicate increases of accumulation and redistribution of acetate at higher doses.

Acetate elimination during ethanol oxidation obeys capacity-limited kinetics.