A PHARMACOKINETIC PHARMACODYNAMIC COMPARISON OF SAAM-II AND PC/WINNONLIN MODELING SOFTWARE/

This paper presents a detailed comparison of the kinetic analysis soft ware packages SAAM II and PCNonlin/WinNonlin, based on benchmark model ing problems reported in ''Pharmacokinetic and Pharmacodynamic Data An alysis: Concepts and Applications'' (Gabrielsson and Weiner, 1994) and seven additional models. For each model, both software packages were presented with identical implementations, Models were initially execut ed in PCNonlin or WinNonlin and automated comparisons with SAAM II mad e using Microsoft Test, Models investigated included one- and multicom partment models with nonlinearities, multiple inputs and samples, mult iple simultaneous experiments, and linear equations. Maximum number of compartments, data sets, and parameters were 9, 5, and 10, respective ly. We compared 88 different models, many of them in different configu rations, e.g., different weighting schemes or different parameter limi ts. The total number of attempted comparisons between SAAM II and PCNo nlin was 161, of which 142 executed without problems. Parameter estima tes, their precision (standard errors), and model predictions were com pared; a difference of 1% or less was considered ''agreement''. Observ ed differences, mainly in parameter standard errors, can be accounted for in terms of different optimization algorithms, convergence criteri a, and individual capabilities. In general, there was good agreement ( <1% difference) between SAAM II and PCNonlin in terms of parameter est imates and model predictions. However, due to differences in the optim ization procedure, parameter standard errors showed considerable diffe rences. Additionally, there were differences when multiple data sets w ere fitted, indicating the importance of different fitting procedures for interpreting multiple kinetic data sets. The full results of the c omparison and the model files in SAAM II and PCNonlin/WinNonlin format s are available from the authors.