2006 - Brugge/Bruges - Belgium

PAGE 2006: Software demonstration
Justin Wilkins

Xpose – an R-based population pharmacokinetic/pharmacodynamic model-building aid for NONMEM

Wilkins, Justin J (1), Hooker, Andrew (1), Karlsson, Mats O (1), Jonsson, E Niclas (2)

(1) Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden (2) F. Hoffman La-Roche, PDMP 15/1.052, Grenzacherstrasse 124, CH-4070 Basel, Switzerland

The building of population pharmacokinetic/pharmacodynamic (PK/PD) models is a time-consuming and complicated task. To some degree, this has been made easier in recent years by the introduction of a number of software tools designed to facilitate data exploration and visualization (1), project organization (2), and model evaluation (3, 4), amongst others.

We present the fourth official release of Xpose, an open-source model-building aid for population analysis using NONMEM. It provides a toolkit for dataset checkout, exploration and visualization, model diagnostics, candidate covariate identification and model comparison. We have incorporated a number of improvements since the last release, particularly with respect to the implementation of recent advances in model diagnostic techniques. One such advance is in the increasing use of simulation: Xpose now provides ‘mirror’ functionality for the majority of its diagnostic plots, in which observed and simulated data may be displayed simultaneously. In addition, Xpose now sports a fully object-oriented, modular design, allowing the analyst to use system functions and plots outside of the classic menu system, both from the host software command line, and from within other tools such as Census. Full control over graphical styles is now available in a fast and intuitive manner, much shortening the time needed to produce publication-quality graphics with the software.

Finally, Xpose has been migrated from S-PLUS to the open-source statistical environment R, enabling its use in a far wider range of environments than was possible previously. The modularity and flexibility of Xpose, coupled with the free availability of programming interfaces to its host, R, give it the potential to be a powerful, general-purpose graphics engine for population PK/PD data analysis.

1. Jonsson EN, Karlsson MO. Xpose--an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Comput Methods Programs Biomed. 1999 Jan;58(1):51-64.
2. Wilkins JJ. NONMEMory: a run management tool for NONMEM. Comput Methods Programs Biomed. 2005 Jun;78(3):259-67.
3. Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN)--a Perl module for NONMEM related programming. Comput Methods Programs Biomed. 2004 Aug;75(2):85-94.
4. Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit--a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 2005 Sep;79(3):241-57.

Reference: PAGE 15 (2006) Abstr 1031 [www.page-meeting.org/?abstract=1031]
Software demonstration