Whole-body PBPK model of valproic acid including non-linear binding with albumin in adults, children and children with hypoalbuminemia. This repository contains:
- a PK-Sim snapshot (*.json ) file of the current PBPK model
- static content (*.md files) as inputs for an evaluation plan
- an evaluation plan (evaluation-plan.json) to create an evaluation report using the snapshot and static text blocks to display the performance of the model This PBPK model is intended to be used as a basis for the implementation of non-linear protein binding using PBPK/Mobi. The PBPK model helped assess the nonlinear dose-exposure relationship of VPA and the impact of albumin concentrations on the achievement of target exposure. This whole-body PBPK model of valproic acid has been developed using in published information and the parameters were optimized based on pharmacokinetic clinical data.
The model has then been evaluated simulating a large number of clinical studies and comparing with respective observed data, obtained from published clinical pharmacokinetic studies.
This model has been published1.
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The model code is distributed under the GPLv2 License.
[1] Karatza, E., Sinha, J., Maglalang, P. D., Edginton, A., & Gonzalez, D. (2024). Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia. Clinical pharmacokinetics, 63(10), 1435–1448. https://doi.org/10.1007/s40262-024-01418-8