Iterative least-squares fitting programs in pharmacokinetics for a programmable handheld calculator

Abstract

Programs that perform a nonlinear least-squares fit to data conforming to one-compartment oral or two-compartment intravenous pharmacokinetic models are described. The programs are designed for use on a Hewlett-Packard HP-41 CV programmable calculator equipped with an extended-functions module and one or two extended-memory modules. Initial estimates of variables in the model are calculated by the method of residuals and then iteratively improved by the use of the Gauss-Newton algorithm as modified by Hartley. This modification minimizes convergence problems. The iterative-fitting procedure includes a routine for estimation of lag time for the one-compartment oral model. Clinical applications of the programs are illustrated using previously published data. Programming steps and user instructions are listed. The programs provide an efficient and inexpensive method of estimating pharmacokinetic variables.