T Fujimiya1, Y J Li, K Uemura, Y Ohbora. 1. Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan. fujimiya@basic.kpu-m.ac.jp
Abstract
BACKGROUND: Acetate redistribution from hepatic to peripheral tissues was reported during ethanol metabolism when saturating conditions were reached for acetate metabolism. Because this redistribution cannot be clarified by linear kinetics, elimination kinetics of acetate was studied in the rabbit. METHODS: A sodium-acetate solution in physiological saline (0.5 and 1.0 g/kg of body weight) was injected as an intravenous bolus. The blood acetate profile was measured by headspace gas chromatography. RESULTS: Blood acetate disappeared rapidly. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve and the mean residence time increased with an increasing dose amount. These increases suggested a capacity-limited elimination of acetate. Simultaneous multilines fitting after two acetate doses was used to estimate the pharmacokinetic model by the application of minimum Akaike's information criterion estimation. As a result, the blood acetate concentration-time curve was best described by a two-compartment open model with Michaelis-Menten elimination kinetics. The Vmax value was approximately two times larger than that of ethanol obtained by using the same compartment model. The Km value (1.5 mM) was almost the same as that of ethanol and corresponded to blood acetate levels during ethanol oxidation that had been reported to be approximately 2 mM. CONCLUSION: The elimination of acetate obeys nonlinear kinetics, which can clarify the saturation of acetate metabolism.
BACKGROUND:Acetate redistribution from hepatic to peripheral tissues was reported during ethanol metabolism when saturating conditions were reached for acetate metabolism. Because this redistribution cannot be clarified by linear kinetics, elimination kinetics of acetate was studied in the rabbit. METHODS: A sodium-acetate solution in physiological saline (0.5 and 1.0 g/kg of body weight) was injected as an intravenous bolus. The blood acetate profile was measured by headspace gas chromatography. RESULTS: Blood acetate disappeared rapidly. Statistical moment analysis of the blood acetate profiles showed that the normalized area under the curve and the mean residence time increased with an increasing dose amount. These increases suggested a capacity-limited elimination of acetate. Simultaneous multilines fitting after two acetate doses was used to estimate the pharmacokinetic model by the application of minimum Akaike's information criterion estimation. As a result, the blood acetate concentration-time curve was best described by a two-compartment open model with Michaelis-Menten elimination kinetics. The Vmax value was approximately two times larger than that of ethanol obtained by using the same compartment model. The Km value (1.5 mM) was almost the same as that of ethanol and corresponded to blood acetate levels during ethanol oxidation that had been reported to be approximately 2 mM. CONCLUSION: The elimination of acetate obeys nonlinear kinetics, which can clarify the saturation of acetate metabolism.