Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy

Silva, Rui; Colom, Helena; Bicker, Joana; Almeida, Anabela; Silva, Ana; Sales, Francisco; Santana, Isabel; Falcão, Amílcar; Fortuna, Ana

doi:10.3390/pharmaceutics15061704

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…Therapeutic drug monitoring (TDM) is an essential tool to address this complexity, enabling the definition of individual therapeutic concentrations and adaptive control of dosing to minimize drug interactions and prevent loss of efficacy or toxicity ( Krasowski, 2010 ). Some studies have shown that PER plasma levels were affected by otherAEDs in routine TDM practice, including carbamazepine, phenobarbital, valproate and topiramate ( Patsalos et al, 2016 ; Contin et al, 2018 ; Silva et al, 2023 ). A recent study indicated that enzyme-inductive AED could increase PER clearance ( Fujita et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy

Yu,

Chen,

Liu

et al. 2023

Front. Pharmacol.

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Perampanel is a promising option for the treatment of pediatric epilepsy, but its plasma concentration varies among patients. This retrospective study aimed to investigate the initial target attainment of perampanel plasma concentration in pediatric patients with epilepsy in China. Inpatients admitted from January 2020 to December 2021 in a tertiary hospital were retrospectively included according to pre-set criteria. Demographic characteristics of patients and dosing strategies and therapeutic drug monitoring results were collected. A total of 137 pediatric patients (84 females and 53 males, aged from 0.6 to 16.4 years) were include for analysis. The perampanel concentrations varied greatly from 60 to 1,560 mg/L among patients, but 89.8% had suitable perampanel concentrations (100–1,000 ng/mL). The concomitant use of enzyme-inductive antiepileptic drugs (AEDs) was the only identified risk factor associated with target nonattainment (OR = 5.92, 95% confidence interval 1.68–20.9). Initial perampanel target attainment in pediatric patients is satisfactory. Routine therapeutic drug monitoring to achieved the suggested concentration range for these patients may be unnecessary, except for those receiving combined enzyme inductive AEDs.

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Section: Introductionmentioning

confidence: 99%

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy

Yu,

Chen,

Liu

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

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Population pharmacokinetics and dosing optimization of perampanel in children with epilepsy: A real‐world study

Li,

Yi,

Tuo

et al. 2024

Epilepsia

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ObjectiveThe purposes of this study were to explore the pharmacokinetics of perampanel (PER) in children with epilepsy, identify factors that contribute to pharmacokinetic variations among subjects, evaluate the connection between PER exposure and clinical outcome, and establish an evidence‐based approach for tailoring individualized antiepileptic treatment in this specific population.MethodsIn this prospective study, PER plasma concentrations and genetic information on metabolic enzymes were obtained from 194 patients younger than 18 years. The disposition kinetics of PER in pediatric patients following oral dosing were characterized using nonlinear mixed effect models. The effective range for the plasma concentration of PER was determined by assessing the efficacy and safety of PER treatment and analyzing the relationship between drug exposure and clinical response. Monte Carlo simulations were then performed to evaluate and optimize the current dosing regimens.ResultsThe pharmacokinetic profile of PER was adequately described by a one‐compartment model with first‐order absorption and elimination. Body weight, total bilirubin level, and concomitant oxcarbazepine were found to have significant influences on PER pharmacokinetics. Model estimates of apparent clearance and volume of distribution were .016 ± .009 L/h/kg and 1.47 ± .78 L/kg, respectively. The effective range predicted from plasma concentration data in responders was 215–862 μg/L. Dosing scenarios stratified according to essential covariates were proposed through simulation analysis.SignificanceIn this study, we captured the pharmacokinetic/pharmacodynamic characteristics of PER in pediatric epilepsy patients through analysis of real‐world data and adopted a pharmacometric approach to support an individualized dosing strategy for PER in this specific population.

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Population Pharmacokinetic Analysis of Perampanel in Portuguese Patients Diagnosed with Refractory Epilepsy

Cited by 2 publications

References 52 publications

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy

Population pharmacokinetics and dosing optimization of perampanel in children with epilepsy: A real‐world study

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