Estimating the kinetic parameters for enzymatic drug metabolism in the whole animal.

A method for estimating the Michaelis constant, Km, and the maximum reaction velocity, Vmax, for the enzymatic degradation of a parent compound to a metabolite in the intact animal is presented. The technique involves a mathematical analysis which has shown that under specific conditions the peak/plateau blood concentrations of metabolite are related to initial parent compound concentration by the Michaelis-Menten relationship. It has also been shown how these data can be analysed with the "direct linear plot" of Eisenthal and Cornish-Bowden (Biochem. J. 139, 715 (1974)) to yield the enzyme kinetic parameters.