Pharmacokinetic study of ethanol after oral administration: a new approach to enzymatic elimination.

ABSTRACT

A new approach to the enzymatic elimination of ethanol in vivo allows us by means of a one-compartment model to take into account all the phases of the ethanol concentration-time curve after oral administration. The Michaelis-Menten equation is an approximation of this model; indeed it constituted the only non-linear approach to the kinetic study of ethanol. To express the model in the form of an equation leads to a third-order system of bilinear differential equations which has no analytical solution. The identification of the model is based on the optimization of a conformity criterion between experimental values and those predicted by the model. Optimization is performed by means of an iterative algorithm minimizing non-linear functions. This method permits the estimation of initial concentrations of products involved in the enzymatic reaction (substrate, enzyme) and kinetic constants (characterizing absorption and enzymatic reaction). Kinetics in nonalcoholics, alcoholics, and former alcoholics were identified using this new model. A good fit between the experimental values and the simulated curve was obtained. The in vivo estimation of the kinetic constants of each elementary step of the enzymatic reaction represents an original approach likely to provide more knowledge of ethanol metabolism.