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Development and Validation of Linear Regression Models to Predict Plasma-Free Perampanel Concentrations Using Routine
Rena Yamaguchi1, Tatsuya Yagi1, Toshiaki Suzuki1
1Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Therapeutic Drug Monitoring
|May 28, 2026
Summary
This study developed two models to estimate free perampanel concentration (Cpf) using routine clinical data, aiding therapeutic drug monitoring of this antiseizure medication when direct Cpf measurement is not feasible.
Area of Science:
- Pharmacology
- Clinical Chemistry
- Drug Monitoring
Background:
- Perampanel is an antiseizure medication with high protein binding, making total plasma concentration (Cpt) a less direct indicator of effect than free concentration (Cpf).
- Measuring Cpf is analytically challenging and not standard in clinical practice.
- Routine clinical data can potentially be used to estimate Cpf.
Purpose of the Study:
- To develop practical models for estimating free perampanel concentration (Cpf) using readily available clinical data.
- To provide a feasible method for therapeutic drug monitoring of perampanel.
Main Methods:
- A prospective, observational study involving adult patients receiving perampanel.
- Quantification of Cpf and Cpt using liquid chromatography-tandem mass spectrometry after ultrafiltration for Cpf.
- Development of two linear regression models: one using Cpt and another using daily dose, with internal validation.
Main Results:
- Model 1 (Cpt-based) incorporating serum creatinine and treatment duration showed strong performance (adjusted R2 = 0.808).
- Model 2 (dose-based) incorporating interleukin-6 showed moderate performance (adjusted R2 = 0.662).
- Both models exhibited good internal validity, with predicted Cpf correlating well with observed values.
Conclusions:
- Two linear regression models were successfully developed to estimate unbound perampanel concentration (Cpf) from routine clinical data.
- These models offer a practical solution for therapeutic drug monitoring of perampanel, especially when direct Cpf measurement is not possible.
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