Method for Estimating Rate Constants for Absorption, Metabolism, and Elimination from Urinary Excretion Data

Abstract

A method is described for estimating the first-order rate constants for absorption, metabolite formation, and all-over loss of drug from the body if the time course of urinary excretion of the metabolite and an estimate of the rate constant for urinary excretion of the metabolite are available. The rate constants are estimated by drawing only two graphs and performing simple calculations which are described in detail. A simulation example is given where the rate constants were estimated with small errors when the rate constant for absorption was only twice the magnitude, and the rate constant for urinary excretion of metabolite only three times the magnitude of the rate constant for over-all loss of drug from the body. If the estimate of the rate constant for urinary excretion of metabolite is appreciably in error, the other rate constants are estimated with sufficient accuracy that they may be used as preliminary estimates for iterative computer programs which provide “least squares” fitting and which estimate all parameters simultaneously.