Ordinary Differential Equation PK/PD Models Using the SAS Macro NLINMIX

We describe some theory and recent enhancements for the SAS macro NLINMIX (Wolfinger, R. D. ( 1993 ). Laplace's approximation for nonlinear mixed effects models. Biometrika 80:791-795) that enable model calculation to take place within the interaction matrix language SAS/IML (SAS Institute Inc. ( 1999a ). SAS/IML User's Guide Version 7. Cary, NC: SAS Institute Inc.). They provide greater flexibility and scope for the specification and analysis of complex nonlinear mixed models. For example, using data from a frequently sampled intravenous glucose test, we fit a two-compartment kinetics model that has no closed-form representation. It is derived as the solution of a system of ordinary differential equations and specified as such in SAS/IML. Additional details and example NLINMIX code are available in Appendix A.