NONMEM package

The NONMEM package continues to be the most widely used software for population-based PK/PD analysis. Its limitations lie mostly with its user interface, which, despite the numerous modifications to the code including the NM-TRAN preprocessor, remains a warehouse of FORTRAN 77 subroutines. Several alternatives to NONMEM are currently available and others are still under development. It is beyond the scope of this chapter to compare the details of the software itself, nor is it practical given short lifetime of each release. Aarons - has recently reviewed and critiqued the currently available software for population pharmacokinetic analysis. 

Estimation of nonlinear mixed effects models has been implemented in a number of software packages and includes different estimation methods [12]. As NONMEM is the most commonly used software to estimate population parameters this program is base for the following description. 

Implementation of models in all of the above-mentioned packages is not an easy task and requires some experience. With the exception of NONMEM and WINNONMIX, it is also very difficult to implement complete dosing histories into the programs. In addition, the packages are good for parameter estimation. A flexible and straightforward simulation afterwards is difficult and also requires some experience. 

Perhaps the area where PopPK has made the largest impact is in drug development. Prior to the introduction of NONMEM as a commercial software package, there was little one could do with pharmacokinetic data collected from Phase 3 clinical studies beyond, perhaps, summary statistics and correlations between some summary measure of the pharmacokinetic data, like the mean or median concentration in a subject, and subject... 

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