Bruno R, Iliadis A, Botta A, Mariotti B, Jullien G, Cano J P
Int J Clin Pharmacol Ther Toxicol. 1983 Jul;21(7):363-9.
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.
一种体内酶促消除乙醇的新方法，使我们能够借助单室模型来考虑口服给药后乙醇浓度-时间曲线的所有阶段。米氏方程是该模型的一种近似；实际上，它是乙醇动力学研究中唯一的非线性方法。将该模型表示为方程形式会得到一个无解析解的三阶双线性微分方程组。模型的识别基于对实验值与模型预测值之间一致性标准的优化。通过最小化非线性函数的迭代算法进行优化。该方法允许估计酶促反应中涉及的产物（底物、酶）的初始浓度和动力学常数（表征吸收和酶促反应）。使用这个新模型确定了非酗酒者、酗酒者和既往酗酒者的动力学。实验值与模拟曲线之间获得了良好的拟合。酶促反应每个基本步骤的动力学常数的体内估计代表了一种可能提供更多乙醇代谢知识的原始方法。
