A new algorithm for computing the parameters of linear compartment models in pharmacokinetics

Abstract

A new algorithm (FADHA) for computing pharmacokinetic parameter estimates has been developed. This technique is based on the simplex method which is used to minimize a nonlinear cost function. An important property of this program is that the convergence is ensured contrary to the well-known linear or nonlinear least-squares regression analysis which lead to a lack of convergence or to a false one. Two investigations of the comparative performances of FADHA program and other algorithms were undertaken (hexamethylmelamine and Piracetam pharmacokinetics). Least square analysis of data yielded biased estimates whereas FADHA estimates were unbiased and more precise. This new technique, takes into account all the possible observation errors and uses the concept of a weighting function rather than weights as such.