Trial reportBritish journal of clinical pharmacology2007
Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues.
Trial report in British journal of clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01656161 (A Multicentre, Open, Non-comparative, Phase III Study on the Efficacy, Pharmacokinetics, and Safety of Two Subcutaneous Injections of Triptorelin Embonate 22.5 mg 6-month Formulation in Patients With Advanced Prostate Cancer), which is not on this map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicentre, Open, Non-comparative, Phase III Study on the Efficacy, Pharmacokinetics, and Safety of Two Subcutaneous Injections of Triptorelin Embonate 22.5 mg 6-month Formulation in Patients With Advanced Prostate Cancer
Who cites it
17 citing papers in PubMed.
- Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects.CPT: pharmacometrics & systems pharmacology · 2018Trial
- A semi-mechanistic integrated pharmacokinetic/pharmacodynamic model of the testosterone effects of the gonadotropin-releasing hormone agonist leuprolide in prostate cancer patients.Clinical pharmacokinetics · 2015Trial
- Early stage development of the glycine-1 re-uptake inhibitor SCH 900435: central nervous system effects compared with placebo in healthy men.British journal of clinical pharmacology · 2013Trial
- Identification of the primary mechanism of action of an insulin secretagogue from meal test data in healthy volunteers based on an integrated glucose-insulin model.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study.Clinical drug investigation · 2009Trial
- Stochastic Differential Equations (SDEs) in NONMEM for Probing Population Pharmacokinetic Model Misspecification: Diagnostic Utility, Practical Considerations, and Future Directions.The AAPS journal · 2026Article
- Population PK and Semimechanistic PK/PD Modeling and Simulation of Relugolix Effects on Testosterone Suppression in Men with Prostate Cancer.Clinical pharmacology and therapeutics · 2023Article
- Quantitative approaches in clinical reproductive endocrinology.Current opinion in endocrine and metabolic research · 2022Review
- Linking categorical models for prediction of pleasantness score using individual predictions of sweetness and creaminess: An advancement of categorical modeling.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Population pharmacokinetic-pharmacodynamic modelling of the relationship between testosterone and prostate specific antigen in patients with prostate cancer during treatment with leuprorelin.British journal of clinical pharmacology · 2019Article
- Handling interoccasion variability in model-based dose individualization using therapeutic drug monitoring data.British journal of clinical pharmacology · 2019Article
- Optimal dynamic control approach in a multi-objective therapeutic scenario: Application to drug delivery in the treatment of prostate cancer.PLoS computational biology · 2018Article
- Approaches for modeling within subject variability in pharmacometric count data analysis: dynamic inter-occasion variability and stochastic differential equations.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Population Pharmacokinetic Analysis of Lanreotide Autogel/Depot in the Treatment of Neuroendocrine Tumors: Pooled Analysis of Four Clinical Trials.Clinical pharmacokinetics · 2016Article
- A semi-physiological-based pharmacokinetic/pharmacodynamic model to describe the effects of topotecan on b-lymphocyte lineage cells.Pharmaceutical research · 2010Article
- Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology.Clinical pharmacokinetics · 2008Review
- Semi-mechanistic pharmacodynamic modeling for degarelix, a novel gonadotropin releasing hormone (GnRH) blocker.Journal of pharmacokinetics and pharmacodynamics · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin and the GnRH receptor blocker degarelix.
methodsFifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis.
resultsIn our final PK/PD model of the HPG axis, the half-life of LH was estimated to be 1.3 h and that of testosterone 7.69 h, which corresponds well with literature values. The estimated potency of LH with respect to testosterone secretion was 5.18 IU l(-1), with a maximal stimulation of 77.5 times basal testosterone production. The estimated maximal triptorelin stimulation of the basal LH pool release was 1330 times above basal concentrations, with a potency of 0.047 ng ml(-1). The LH pool release was decreased by a maximum of 94.2% by degarelix with an estimated potency of 1.49 ng ml(-1).
conclusionsOur model of the HPG axis was able to account for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.