Therapeutic Drug Monitoring of Perampanel in Children With Refractory Epilepsy: Focus on Influencing Factors on the
Rui Qu1,2, Yuanyuan Dai2, Zengyan Zhu3
1Department of Neurology, Children's Hospital of Soochow University, Suzhou Industrial Park, Jiangsu Province, China.
Insights
This study examined perampanel pharmacokinetics in children with refractory epilepsy. Drug interactions with oxcarbazepine and valproic acid significantly altered perampanel levels, while inflammation increased them.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Pediatric Neurology
Background:
- Refractory epilepsy in children presents treatment challenges.
- Perampanel is an adjunctive therapy for epilepsy.
- Understanding perampanel pharmacokinetics is crucial for effective treatment.
Purpose of the Study:
- To evaluate the impact of dose, age, sex, and comedications on steady-state free-perampanel concentration in pediatric refractory epilepsy.
- To investigate the relationship between inflammation and perampanel pharmacokinetics.
Main Methods:
- Prospective study of 87 children with refractory epilepsy on adjunctive perampanel.
- Plasma free and total perampanel concentrations measured by liquid chromatography-tandem mass spectrometry.
- Analysis of factors influencing free-perampanel concentration, including comedications and inflammation markers.
Main Results:
- Mean free-perampanel concentration was 5.7 ± 2.7 ng/mL.
- Oxcarbazepine reduced the free concentration-to-dose ratio by 37%; valproic acid increased it by 52%.
- Inflammation (elevated Hs-CRP) increased perampanel levels; age and sex had no significant effect.
Conclusions:
- Perampanel exhibits complex pharmacokinetic interactions with other antiseizure medications.
- Clinicians should consider drug interactions and inflammation when prescribing perampanel.
- Quantifying both total and free perampanel concentrations aids in assessing pharmacokinetic interactions.
Background:
This study aimed to assess the effect of perampanel dose, age, sex, and antiseizure medication cotherapy on steady-state free-perampanel concentration in children with refractory epilepsy, as well as the relationship between inflammation and the pharmacokinetics of perampanel.
Methods:
This prospective study in China included 87 children with refractory epilepsy treated with adjunctive perampanel therapy. Free and total perampanel concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Free-perampanel concentration was compared among patients with various potential influencing factors.
Results:
A total of 87 pediatric patients (44 female children) aged 2-14 years were enrolled. The mean free-perampanel concentration and free concentration-to-dose (CD) ratio in plasma were 5.7 ± 2.7 ng/mL (16.3 ± 7.7 nmol/L) and 45.3 ± 21.0 (ng/mL)/(mg/kg) [129.6 ± 60.1 (nmol/L)/(mg/kg)], respectively. The protein binding of perampanel in plasma was 97.98%. A linear relationship was observed between perampanel dose and free concentration in plasma, and a positive relationship was found between the total and free-perampanel concentrations. Concomitant use of oxcarbazepine reduced the free CD ratio by 37%. Concomitant use of valproic acid increased the free CD ratio by 52%. Five patients had a plasma high-sensitivity C-reactive protein (Hs-CRP) level of >5.0 mg/L (Hs-CRP positive). The total and free CD ratios of perampanel were increased in patients with inflammation. Two patients with inflammation developed adverse events, which disappeared as the Hs-CRP level returned to normal, and neither required perampanel dose reduction. Age and sex did not influence the free-perampanel concentration.
Conclusions:
This study found complex drug interactions between perampanel and other concomitant antiseizure medications, providing valuable information to enable clinicians to apply perampanel in the future reasonably. In addition, it may be important to quantify both the total and free concentrations of perampanel to assess complex pharmacokinetic interactions.
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