Non-linear mixed-effects pharmacokinetic/pharmacodynamic modelling in NLME using differential equations
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Updated: Aug 23, 2026

Development of an Individual-Tree Basal Area Increment Model using a Linear Mixed-Effects Approach
Published on: July 3, 2020
Christoffer W Tornøe1, Henrik Agersø, E Niclas Jonsson
1Experimental Medicine, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, DK-2300 Copenhagen S, Denmark. christoffer.tornoe@ferring.com
Abstract:
The standard software for non-linear mixed-effect analysis of pharmacokinetic/pharmacodynamic (PK/PD) data is NONMEM while the non-linear mixed-effects package NLME is an alternative as long as the models are fairly simple. We present the nlmeODE package which combines the ordinary differential equation (ODE) solver package odesolve and the non-linear mixed effects package NLME thereby enabling the analysis of complicated systems of ODEs by non-linear mixed-effects modelling. The pharmacokinetics of the anti-asthmatic drug theophylline is used to illustrate the applicability of the nlmeODE package for population PK/PD analysis using the available data analysis tools in R for model inspection and validation. The nlmeODE package is numerically stable and provides accurate parameter estimates which are consistent with NONMEM estimates.
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