Non-linear mixed-effects pharmacokinetic/pharmacodynamic modelling in NLME using differential equations

Christoffer Wenzel Tornøe, Henrik Agersø, Henrik Madsen, E. Niclas Jonsson, Henrik Aalborg Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review


    The standard software for non-linear mixed-effect analysis of pharmacokinetic/phar-macodynamic (PK/PD) data is NONMEM while the non-linear mixed-effects package NLME is an alternative as tong 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. (C) 2004 Elsevier Ireland Ltd. ALL rights reserved.
    Original languageEnglish
    JournalComputer Methods and Programs in Biomedicine
    Issue number1
    Pages (from-to)31-40
    Publication statusPublished - 2004


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