An analysis program MULTI(ELS) based on extended nonlinear least squares method for microcomputers

Abstract

An analysis program MULTI(ELS) was developed for population pharmacokinetics on a microcomputer. The program based on the extended least squares (ELS) is written in the Microsoft minimum BASIC command alone. ELS simultaneously estimates not only the population pharmacokinetic parameters but also the variances of inter-individual variabilities around the population parameters and of intra-individual variabilities for the plural time courses, whereas the ordinary least squares estimates the pharmacokinetic parameters of each time course. Two least squares algorithms (i.e. quasi-Newton and simplex methods) are provided in MULTI(ELS). MULTI(ELS) was compared with NONMEM (Version I, Level 3) developed by Sheiner and Beal for several time course data. It was shown that MULTI(ELS) gave the same results as NONMEM. MULTI(ELS) calculates the Akaike's information criterion (AIC) for the extended least squares. It was also shown that the AIC is effective in comparing the population characteristics of time courses in a group with those in another group and in verifying the model structures of population means, inter-individual variations and intra-individual variations.