@ARTICLE\{IMM2004-03932,
    author       = "C. W. Torn{\o}e and H. Agers{\o} and H. A. Nielsen and H. Madsen and E. N. Jonsson",
    title        = "Pharmacokinetic/Pharmacodynamic Modelling of GnRH Antagonist Degarelix: A Comparison of the Non-linear Mixed-Effects Programs {NONMEM} and {NLME}",
    year         = "2004",
    keywords     = "population pharmacokinetic/pharmacodynamic modelling; non-linear mixed-effects programs; {NONMEM}; {NLME}; degarelix; GnRH antagonist.",
    pages        = "441-461",
    journal      = "Journal of Pharmacokinetics and Pharmacodynamics",
    volume       = "31",
    editor       = "",
    number       = "6",
    publisher    = "",
    url          = "http://www2.compute.dtu.dk/pubdb/pubs/3932-full.html",
    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."
}