Historically, a number of different software packages running on a variety of hardware platforms have been used for model simulation. SimuSolv found wide use because of its broad capabilities, including optimization, statistical analysis, and formalized sensitivity analysis as well as the capacity to incorporate user-supplied subroutines. However, in the early 1990s, SimuSolv development ceased and a final version was released in 1993. Thus SimuSolv will not be developed for newer platforms and operating systems. In this article, we compare and contrast the use of SimuSolv and Matlab (The MathWorks, Natick, MA) for physiologically based pharmacokinetic (PBPK) model implementation with respect to parameter estimation (optimization) and sensitivity analysis using a PBPK model for trichloroethylene (TCE). In both packages, it is possible to code PBPK models, run simulations, estimate parameters, and do sensitivity analysis.The key difference is the additional programming required in Matlab. Since Matlab does...