Handling missed dose of riluzole by population pharmacokinetic model informed remedial regimen
Year: 2026
Type: article
Abstract: Background: Patients with amyotrophic lateral sclerosis (ALS) frequently exhibit nonadherence characterized by delayed or missed doses while taking riluzole. This study aimed to provide a population pharmacokinetic (PPK) model informed individualized remedial regimens for patients who experience delayed or missed doses of riluzole. Methods: A PPK model for riluzole was developed via a nonlinear mixed-effect modeling approach based on 3,024 concentration-time points from 72 subjects. The final model was validated by multiple methods. Six remedial regimens for missed doses were simulated for concentration-time profiles under different scenarios, and the optimal remedial regimen was selected based on the least time of concentration beyond the normal range. Results: /F and Q were 67 L/h, 242 L, 376 L and 33.1 L/h, respectively. The model was showed acceptable performance by goodness-of-fit, visual predictive check, bootstrap analysis and normalized distribution prediction errors. Model-based remedial regimens for different missed scenarios were proposed. Conclusion: A riluzole PPK model was developed and internally evaluated using multiple diagnostic approaches. Model-based remedial dosing strategies for different missed-dose scenarios were identified based on predefined PK criteria and Monte Carlo simulations. These exploratory strategies provide quantitative insights into riluzole exposure during nonadherent dosing conditions.
Source: Frontiers in Pharmacology
Authors: Changlong Liu, Qing Tang, Lingyan Yu, Zhenwei Yu
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7214930828