Effect of valproic acid on perampanel pharmacokinetics in patients with epilepsy

Contin, Manuela; Bisulli, Francesca; Santucci, Margherita; Riva, R.; Tonon, Francesca; Mohamed, Susan; Ferri, Lorenzo; Stipa, Carlotta; Tinuper, Paolo

doi:10.1111/epi.14446

Cited by 27 publications

(29 citation statements)

References 14 publications

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“…The combination of perampanel with enzyme inducers significantly reduced perampanel C/D. The mean values of C/D were similar in patients treated with carbamazepine, phenytoin, or oxcarbazepine 14…”

Section: Resultsmentioning

confidence: 82%

“…A second study on pharmacokinetics was found in our literature review. It was a multicenter, open, prospective study on the effects of antiepileptic drugs on the steady-state plasma concentration of perampanel in epilepsy patients 14. Patients aged 12 years and over treated with a stable dose of perampanel for at least 1 month and stable concomitant antiepileptic drugs for the last 3 weeks were included.…”

Section: Resultsmentioning

confidence: 99%

“…Patients aged 12 years and over treated with a stable dose of perampanel for at least 1 month and stable concomitant antiepileptic drugs for the last 3 weeks were included. Blood samples were collected approximatively 12 hrs after perampanel intake at bedtime to evaluate the perampanel plasma concentration to weight‐adjusted daily dose ratio as the main primary outcome (C/D; [μg/mL]/mg kg −1 d −1 ) 14. This study reported the data from 114 blood samples from 79 patients (53% female) with a mean age of 33 ± 13 years with a body weight of 68 ± 21 kg.…”

Section: Resultsmentioning

confidence: 99%

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<p>An Evidence-Based Review On The Use Of Perampanel For The Treatment Of Focal-Onset Seizures In Pediatric Patients</p>

Dozières‐Puyravel¹,

Auvin²

2019

NDT

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Perampanel, a non-competitive AMPA receptor antagonist, is a once-daily oral antiepileptic drug approved for the treatment of focal seizures and primary generalized tonicclonic seizures in children 12 years of age and over. We conducted a systematic review of the data on perampanel in children and adolescents with focal-onset seizures. We found 21 published papers on the pediatric use of perampanel for focal-onset seizures, including 9 papers on clinical trials and ancillary studies of these trials, of which 2 focused on pharmacokinetics, 1 was a metaanalysis, and 9 were real-life studies (1 was prospective). Perampanel, as an adjunctive treatment for uncontrolled focal-onset seizures, results in an improvement of seizure control with a generally good safety profile. Evidence-based data are currently available for children 12 years of age and over. Higher amounts of perampanel might be required in patients taking enzymeinducing antiepileptic drugs. The most common adverse events are somnolence, dizziness and behavioral adverse events. The latter seems more frequent in adolescents than in adults and in adolescents with preexisting behavioral comorbidities. Current studies did not identify any shortterm impact of perampanel on cognitive functions. Its long half-life allows once-daily administration. Real-life studies further established that a decrease of the dose frequently resolves adverse events, as demonstrated in pivotal studies. Pharmacokinetic and safety studies are still ongoing in the younger population, down to 4 years of age, in order to apply for approval in this age group.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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<p>An Evidence-Based Review On The Use Of Perampanel For The Treatment Of Focal-Onset Seizures In Pediatric Patients</p>

Dozières‐Puyravel¹,

Auvin²

2019

NDT

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“…Among the recommendations of the World Health Organization, the advantage in therapy is given to valproate, in the case of a generalized form of epilepsy (Contin et al, 2018). With focal form, carbamazepine is preferred (Sarkis et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Pharmacoepidemiology of Antiepileptic Drugs in Children

2021

pnr

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With the pharmacotherapy of epilepsy, there is a decrease in the number of seizures or their complete cessation. The aim of the study was to conduct a comparative analysis of the efficacy and safety of antiepileptics traditionally used in medicine (valproate, carbamazepine) and new-generation analogs (topiramate) in the treatment of epilepsy in children and adolescents. The study was conducted in 2014 and 2018, at the Center for Epileptology and Neurology, Moscow (Russian Federation). In 2014, 777 medical records of children registered with epileptologists were studied, in 2018 -840 medical records of children. The age interval of 3 months is 18 years. Favorable outcomes of epilepsy therapy with different drugs were calculated, with different approaches monotherapy and polytherapy. A favorable outcome meant remission, which lasted more than 1 year and more than 3 years. In 2014 and 2018, monotherapy prevailed among the treatment methods. With monotherapy, valproates are used more often (up to 70%), carbamazepine is used 3.0 times less often (p ≤ 0.01 relative to valproates). The use of topiramate is 10 times less than the number of valproate therapy (p ≤ 0.0001), and barbiturates -15 times (p ≤ 0.0001). Among the new generation drugs, topiramate was often used, with monotherapy, with symptomatic forms of epilepsy (10.4% in 2014 and 7.9% in 2018, p ≤ 0.05), as well as with a cryptogenic form (9.6% and 4.4%, respectively, p ≤ 0.05). The chosen type of therapy can significantly affect the number of side effects. With polytherapy, in 2014, side effects were observed in 44.1% compared with monotherapy (18.1%, at p ≤ 0.01), in 2018 -45.1% against 20.9% (at p ≤ 0.01). Topiramate showed lower efficacy compared with carbamazepine in all years of the study with monotherapy (0.65, at p ≤ 0.04). The results did not confirm the effectiveness of the new drugs. There was no difference in efficacy and safety between traditional drugs (valproate, carbamazepine) and new generation drugs (topiramate and others). In 2014 and 2018, monotherapy (72.8%) over polytherapy (27.2%) prevailed among the treatment methods for epilepsy. Among the drugs, valproate was predominant (65.8%), and in all identified forms of epilepsy. The new generation of drugs did not show statistically significant advantages compared to traditionally used ones. The method of polytherapy of epilepsy in children gives a twofold increase in the likelihood of side effects (p ≤ 0.01).

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“…Butyrate, phenylbutyrate, and valproic acid belong to the first family and due to their relatively weak activity, and their use for psychiatric diseases are less clinically interesting [110]. The pan-HDAC inhibitors, hydroxymic acids vorinostat, belinostat, and panobinostat, were initially approved by the FDA in early 2000s for the treatment of myelodysplastic syndrome [32].…”

Section: Histone Modifications: Implication and Inhibitionmentioning

confidence: 99%

Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin

Citron

Fabris

2020

Cancers

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Extensive efforts recently witnessed the complexity of cancer biology; however, molecular medicine still lacks the ability to elucidate hidden mechanisms for the maintenance of specific subclasses of rare tumors characterized by the silent onset and a poor prognosis (e.g., ovarian cancer, pancreatic cancer, and glioblastoma). Recent mutational fingerprints of human cancers highlighted genomic alteration occurring on epigenetic modulators. In this scenario, the epigenome dependency of cancer orchestrates a broad range of cellular processes critical for tumorigenesis and tumor progression, possibly mediating escaping mechanisms leading to drug resistance. Indeed, in this review, we discuss the pivotal role of chromatin remodeling in shaping the tumor architecture and modulating tumor fitness in a microenvironment-dependent context. We will also present recent advances in the epigenome targeting, posing a particular emphasis on how this knowledge could be translated into a feasible therapeutic approach to individualize clinical settings and improve patient outcomes.

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Effect of valproic acid on perampanel pharmacokinetics in patients with epilepsy

Cited by 27 publications

References 14 publications

<p>An Evidence-Based Review On The Use Of Perampanel For The Treatment Of Focal-Onset Seizures In Pediatric Patients</p>

<p>An Evidence-Based Review On The Use Of Perampanel For The Treatment Of Focal-Onset Seizures In Pediatric Patients</p>

Pharmacoepidemiology of Antiepileptic Drugs in Children

Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin

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