Tetrahydrobiopterin (BH4) responsiveness in neonates with hyperphenylalaninemia: A semi-mechanistically-based, nonlinear mixed-effect modeling. Assess the individual BH4 responsiveness in neonates suffering from phenylalanine hydroxylase (PAH). It is a pharmacodynamic turnover model (stimulation of loss) of Phenylalanine in blood disposition. The K-PD approach is used to describe BH4 kinetics. Mixture population approach is used to differentiate BH4 sensitive and non-sensitive patients.
Nadia Terranova, Kheizurane_ElMekki
|Context of model development:||Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese);|
|Discrepancy between implemented model and original publication:||The model implemented in the original publication is a mixture model, including two population: sensitive to BH4 ( the SLOP parameter is assumed lognormally distributed) and non-sensitive to BH4 (the SLOP parameter is assumed to be equal to zero).;|
|Long technical model description:||Pharmacodynamic turnover model with stimulation of loss describing the Phenylalanine in blood (Phe) disposition. A K-PD approach was used to describe the kinetics of BH4. The model includes a mixture approaches to distinguish BH4 sensitive to non sensitive patients.;|
|Model compliance with original publication:||No;|
|Model implementation requiring submitter’s additional knowledge:||No;|
|Modelling context description:||Pharmacodynamic model to improve the description of individual sensitivity to BH4 in neonatal period;|
|Modelling task in scope:||estimation;|
|Nature of research:||Clinical research & Therapeutic use;|
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- Additional Files
- Model owner: Nadia Terranova
- Submitted: Dec 11, 2015 4:59:26 PM
- Last Modified: Jul 18, 2016 12:07:40 PM
Independent variable T
Structural Model sm
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Continuous / Residual Data
Estimation Step estimStep_1
Initial estimates for non-fixed parameters
1) Estimate the population parameters