Abstract
The pharmacokinetic behavior of foreign substances that are completely or partially eliminated via metabolism by saturable enzyme systems is analyzed. General integrated equations are derived which describe the time course of the plasma concentration under the assumption of a saturable enzyme system according to Michaelis-Menten kinetics in combination with normal firstorder elimination processes. A procedure for the estimation of initial values of the elementary kinetic parameters on the basis of the models is outlined. These initial values have been used in a nonlinear curvefitting program in order to obtain reliable kinetic and enzyme parameters from the plasma curves. With these methods, kinetic and apparent enzyme parameters are calculated for ethanol, salicylic acid, 4-hydroxybutyric acid, and phenytoin.
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Financial support was provided by the Prevention Fund of the Dutch Ministry of Health and by the Dutch Foundation of Medical Research (Fungo-TNO).
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van Ginneken, C.A.M., van Rossum, J.M. & Fleuren, H.L.J.M. Linear and nonlinear kinetics of drug elimination I. Kinetics on the basis of a single capacity-limited pathway of elimination with or without simultaneous supply-limited elimination. Journal of Pharmacokinetics and Biopharmaceutics 2, 395–415 (1974). https://doi.org/10.1007/BF01071310
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DOI: https://doi.org/10.1007/BF01071310