{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:12:23Z","timestamp":1792811543634,"version":"4.5.0"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the impact of perampanel and demographics on clearance of concomitant antiepileptic drugs (AEDs), in patients with refractory partial\u2010onset seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pooled data from three Phase III clinical studies with adjunctive perampanel were used. Blood samples for evaluation of 11 concomitant AEDs were taken during baseline (before perampanel initiation), and at weeks 10, 14, and 19 during the maintenance phase of perampanel treatment (2\u201312\u00a0mg\/day, once daily at bedtime). Models estimating apparent clearance of each concomitant AED were fitted to the data, and the effects of perampanel and demographic variables on clearance were determined. Final models were assessed with goodness of fit plots including population predictions and individual predictions against observations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant impact of perampanel on clearance was found for clonazepam (<jats:italic>n<\/jats:italic>\u00a0=\u00a081), levetiracetam (<jats:italic>n<\/jats:italic>\u00a0=\u00a0330), phenobarbital (<jats:italic>n<\/jats:italic>\u00a0=\u00a054), phenytoin (<jats:italic>n<\/jats:italic>\u00a0=\u00a090), topiramate (<jats:italic>n<\/jats:italic>\u00a0=\u00a0226) or zonisamide (<jats:italic>n<\/jats:italic>\u00a0=\u00a093). Statistically significant, but small and not clinically relevant increases in model\u2010predicted clearance were detected for carbamazepine (+4.3% with 12\u00a0mg perampanel; <jats:italic>n<\/jats:italic>\u00a0=\u00a0379), clobazam (+3.4% males, +7.7% females, 12\u00a0mg; <jats:italic>n<\/jats:italic>\u00a0=\u00a0114), lamotrigine (+9.3%, 12\u00a0mg; <jats:italic>n<\/jats:italic>\u00a0=\u00a0356), and valproic acid (+5.0%, 12\u00a0mg; <jats:italic>n<\/jats:italic>\u00a0=\u00a0349). Oxcarbazepine clearance was reduced (26%; <jats:italic>n<\/jats:italic>\u00a0=\u00a0200), but the clinical relevance is unclear as levels of the active metabolite (the monohydroxy derivative of oxcarbazepine) were not measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Population PK data show that perampanel (2\u201312\u00a0mg\/day, once daily at bedtime) has no relevant impact on the clearance of the most commonly used concomitant AEDs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12951","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T19:18:58Z","timestamp":1459624738000},"page":"422-430","source":"Crossref","is-referenced-by-count":35,"title":["Impact of perampanel on pharmacokinetics of concomitant antiepileptics in patients with partial\u2010onset seizures: pooled analysis of clinical trials"],"prefix":"10.1111","volume":"82","author":[{"given":"Oneeb","family":"Majid","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Eisai Europe Ltd.  Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Laurenza","sequence":"additional","affiliation":[{"name":"Neuroscience and General Medicine PCU Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Ferry","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Eisai Inc.  Woodcliff Lake New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad","family":"Hussein","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Eisai Europe Ltd.  Hatfield Hertfordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Fycompa Summary of Product Characteristics","author":"Eisai Group","year":"2015"},{"key":"e_1_2_9_3_1","volume-title":"Fycompa US Prescribing Information","author":"Eisai Inc.","year":"2014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182635735"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03638.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318254473a"},{"key":"e_1_2_9_7_1","first-page":"367","article-title":"Adjunctive perampanel (PER) for treatment of drug\u2010resistant primary generalized tonic\u2013clonic (PGTC) seizures in patients (pts) with idiopathic generalized epilepsy (IGE): a double\u2010blind, randomized, placebo\u2010controlled phase III trial","volume":"15","author":"French JA","year":"2015","journal-title":"Epilepsy Curr"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12865"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001558"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12240"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03648.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12643"},{"key":"e_1_2_9_13_1","article-title":"Population pharmacokinetics and pharmacodynamics of perampanel: a pooled analysis from three phase III trials (abstract 2.231)","volume":"12","author":"Laurenza A","year":"2012","journal-title":"Epilepsy Curr"},{"key":"e_1_2_9_14_1","unstructured":"US FDA.Guidance for Industry: Drug interaction studies \u2013 study design data analysis implications for dosing and labeling recommendations 2012. 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