A nonlinear least squares program, MULTI(FILT), based on fast inverse Laplace transform for microcomputers.

Abstract

A nonlinear curve fitting program MULTI(FILT) into which the fast inverse Laplace transform (FILT) is incorporated was developed on a microcomputer. FILT is an algorithm for the numerical inversion of Laplace-transformed equations (image equations) to generate the corresponding real time courses. The pharmacokinetic models can be defined in the form of Laplace-transformed equations as a subroutine in MULTI(FILT). MULTI(FILT) achieves the numerical inversion of the defined image equations according to FILT and the subsequent curve-fitting of the inverse-transformed time courses to the experimental data points to estimate the pharmacokinetic parameters by the nonlinear least-squares method. MULTI(FILT) has a function to impose constraints on the pharmacokinetic parameters. In order to verify the reliability of MULTI(FILT), the pharmacokinetic parameters estimated by MULTI(FILT) were compared with those by MULTI using 100 time courses which were artificially generated according to the Monte Carlo method, based on data for theophylline and bishydroxycoumarin. The estimated pharmacokinetic parameters by MULTI(FILT) agreed with those by MULTI. Thus, it is suggested that FILT, developed in the field of electronic technology, is also useful in the pharmacokinetic field.