Pharmacokinetic/Pharmacodynamic Modelling of GnRH Antagonist Degarelix: A Comparison of the Non-linear Mixed-Effects Programs NONMEM and NLME

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

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    Abstract

    In this paper, the two non-linear mixed-effects programs NONMEM and NLME were compared for their use in population pharmacokinetic/pharmacodynamic (PK/PD) modelling. We have described the first-order conditional estimation (FOCE) method as implemented in NONMEM and the alternating algorithm in NLME proposed by Lindstrom and Bates. The two programs were tested using clinical PK/PD data of a new gonadotropin-releasing hormone (GnRH) antagonist degarelix currently being developed for prostate cancer treatment. The pharmacokinetics of intravenous administered degarelix was analysed using a three compartment model while the pharmacodynamics was analysed using a turnover model with a pool compartment. The results indicated that the two algorithms produce consistent parameter estimates. The bias and precision of the two algorithms were further investigated using a parametric bootstrap procedure which showed that NONMEM produced more accurate results than NLME together with the nlmeODE package for this specific study.
    Original languageEnglish
    JournalJournal of Pharmacokinetics and Pharmacodynamics
    Volume31
    Issue number6
    Pages (from-to)441-461
    ISSN1567-567X
    Publication statusPublished - 2004

    Keywords

    • population pharmacokinetic/pharmacodynamic modelling; non-linear mixed-effects programs; NONMEM; NLME; degarelix; GnRH antagonist.

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