Pharmacokinetic/Pharmacodynamic Modellingof GnRH Antagonist Degarelix: A Comparisonof the Non-linear Mixed-Effects Programs NONMEM and NLME
| 详细信息 | 推荐本文 | |
- 关键词：population pharmacokinetic/pharmacodynamic modelling ; non ; linear mixed ; effects programs ; NONMEM ; NLME ; degarelix ; GnRH antagonist
- 刊名：Journal of Pharmacokinetics and Biopharmaceutics
- 出版时间：December, 2004
- 出版年：2004
- 期刊代码：21_0090466X
- 类别：en
- 卷：31
- 期：6
- 页码：441-461
- 数据来源：sp
摘要
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.