Pharmacokinetics, exposure–cognition, and exposure–efficacy relationships of perampanel in adolescents with inadequately controlled partial-onset seizures

Villanueva, Vicente; Majid, Oneeb; Nabangchang, Charcrin; Huang, Yang; Laurenza, Antonio; Ferry, Jim; Hussein, Ziad

doi:10.1016/j.eplepsyres.2016.08.025

Cited by 24 publications

(34 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A study of the relationship between perampanel exposure and cognitive function found similar pharmacokinetics of perampanel for adolescents (age 12‐17 years) as for adults . In adolescents with focal seizures, increasing perampanel exposure had no significant effect on overall cognition, measured by the CDR System Global Cognition Score, Quality of Working Memory, or Speed of Memory.…”

Section: Perampanel In Clinical Practicementioning

confidence: 97%

“…Because adolescents are in the process of neurological and behavioral change, it is important to establish the impact of AEDs on cognition and development. 77 A phase-2 RCT investigated the cognitive effects of perampanel in 133 adolescents (age 12-17 years) with focal seizures with or without secondary generalization. 78 A study of the relationship between perampanel exposure and cognitive function found similar pharmacokinetics of perampanel for adolescents (age 12-17 years) as for adults.…”

Section: Children and Adolescentsmentioning

confidence: 99%

See 1 more Smart Citation

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

View full text Add to dashboard Cite

This article reviews the profile of perampanel, a novel noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist, and its role as a potential broad-spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase-3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic-clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%-28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%-35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic-clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (-76.5% vs -38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real-world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad-spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.

show abstract

Section: Perampanel In Clinical Practicementioning

confidence: 97%

Section: Children and Adolescentsmentioning

confidence: 99%

Perampanel: Does it have broad‐spectrum potential?

Potschka

Trinka

2018

Epilepsia

View full text Add to dashboard Cite

show abstract

“…Carbamazepine increased the apparent oral clearance of perampanel by approximately threefold . Population PK (PPK) analyses in subjects with POS showed that PK of perampanel was similar in adolescents aged 12–17 years and in adults and perampanel (2–12 mg/day, once daily) had no relevant impact on the clearance of the most commonly used concomitant AEDs …”

mentioning

confidence: 99%

“…10 Carbamazepine increased the apparent oral clearance of perampanel by approximately threefold. 10 Population PK (PPK) analyses in subjects with POS showed that PK of perampanel was similar in adolescents aged 12-17 years and in adults 11,12 and perampanel (2-12 mg/day, once daily) had no relevant impact on the clearance of the most commonly used concomitant AEDs. 13 To date, PK in Korean subjects have been reported only through results of PPK analyses, using nonlinear mixed effect modeling with data from phase 2/3 studies including Korean patients.…”

mentioning

confidence: 99%

Pharmacokinetics of Perampanel in Healthy Korean, White, and Japanese Adult Subjects

Tabuchi

Shiba

Yasuda

et al. 2018

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

Perampanel is a highly selective, orally active, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist that has been approved in many countries as a treatment for partial-onset seizures and primary generalized tonic-clonic seizures. The pharmacokinetics (PK) of perampanel following multiple doses in healthy Korean, white, and Japanese male subjects were assessed in 3 studies. Noncompartmental PK parameters were derived from plasma concentration-time data. At steady state of perampanel 2-, 4-, and 6-mg oral multiple administration, perampanel was rapidly absorbed, as plasma perampanel concentration reached maximum concentration after 0.55-1 hour (median) after dosing in all 3 ethnic groups. The elimination was slow, with terminal elimination phase half-life values ranging from 63.9-129 hours (mean) for doses of 2-6 mg; there was no specific tendency suggesting a dose-related effect, and perampanel PK were linear in Korean subjects. There were no clinically relevant ethnic differences in PK following multiple doses of perampanel 2 and 4 mg between Korean, white, or Japanese subjects. Perampanel was well tolerated by all 3 ethnic groups. This outcome indicates that with respect to PK, the dosing regimens established in white and Japanese patients are applicable to Korean patients.

show abstract

“…In sum, perampanel is a selective, centrally acting, negative allosteric modulator of AMPA receptors with good oral bioavailability and favorable pharmacokinetic properties [10, 11]. A population PK analysis of 152 adolescents aged 12-17 years with refractory partial-onset seizures confirmed that pharmacokinetics of perampanel is similar in adolescents and adults [12]. Perampanel has minimal propensity to cause pharmacokinetic interactions.…”

Section: Pharmacokinetics and Drug Interactionsmentioning

confidence: 99%

Current role of perampanel in pediatric epilepsy

et al. 2017

View full text Add to dashboard Cite

Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.

show abstract

Pharmacokinetics, exposure–cognition, and exposure–efficacy relationships of perampanel in adolescents with inadequately controlled partial-onset seizures

Cited by 24 publications

References 18 publications

Perampanel: Does it have broad‐spectrum potential?

Perampanel: Does it have broad‐spectrum potential?

Pharmacokinetics of Perampanel in Healthy Korean, White, and Japanese Adult Subjects

Current role of perampanel in pediatric epilepsy

Contact Info

Product

Resources

About