{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:48:57Z","timestamp":1790110137651,"version":"4.0.1"},"reference-count":16,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T00:00:00Z","timestamp":1528848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We prospectively examined the effect of antiepileptic (<jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>) cotherapy on steady state plasma concentrations of perampanel (<jats:styled-content style=\"fixed-case\">PMP<\/jats:styled-content>) in epileptic patients. We classified <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>s as strong enzyme inducers (carbamazepine, phenobarbital, phenytoin, oxcarbazepine), not strong enzyme inducers\/not inhibitors (levetiracetam, lamotrigine, topiramate, rufinamide, lacosamide, zonisamide, clobazam), and enzyme inhibitors (valproic acid [<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>]). The main outcome was the comparison of <jats:styled-content style=\"fixed-case\">PMP<\/jats:styled-content> plasma concentration to weight\u2010adjusted dose ratio (C\/D; [\u03bcg\/mL]\/mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0d<jats:sup>\u22121<\/jats:sup>) among comedication subgroups. From 79 patients (42 females, 37 males) aged (mean\u00a0\u00b1 standard deviation) 33\u00a0\u00b1\u00a013\u00a0years (range = 12\u201066\u00a0years), 114 plasma samples were collected. Twenty\u2010eight patients (44 samples) were cotreated with enzyme inducers (group A), 21 (27 samples) with not strong enzyme inducers\/not inhibitors (group B), 21 (31 samples) with not strong enzyme inducers\/not inhibitors + <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> (group C), and 9 (12 samples) with enzyme inducers + <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content> (group D). <jats:styled-content style=\"fixed-case\">PMP<\/jats:styled-content> C\/D was reduced (\u221256%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) in group A (1.79\u00a0\u00b1\u00a00.80) versus group B (4.05\u00a0\u00b1\u00a02.16) and increased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) in group C (6.72\u00a0\u00b1\u00a04.04) compared with groups A (+275%), B (+66%), and D (2.76\u00a0\u00b1\u00a02.00, +143%). Our study documents the unpublished higher <jats:styled-content style=\"fixed-case\">PMP<\/jats:styled-content> C\/D in patients cotreated with <jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>. These findings have both theoretical relevance, suggesting better characterization of <jats:styled-content style=\"fixed-case\">PMP<\/jats:styled-content> metabolic pathways with ad hoc studies, and clinical usefulness in managing patients on <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content> polytherapy.<\/jats:p>","DOI":"10.1111\/epi.14446","type":"journal-article","created":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T14:45:32Z","timestamp":1528901132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effect of valproic acid on perampanel pharmacokinetics in patients with epilepsy"],"prefix":"10.1111","volume":"59","author":[{"given":"Manuela","family":"Contin","sequence":"first","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1109-7296","authenticated-orcid":false,"given":"Francesca","family":"Bisulli","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Santucci","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Riva","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Tonon","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Ferri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Stipa","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tinuper","sequence":"additional","affiliation":[{"name":"Institute of Research and Treatment (IRCCS) Institute of Neurological Sciences of Bologna Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Perampanel Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,13]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Fycompa: summary of product characteristics. London UK: European Medicines Agency;2012."},{"key":"e_1_2_7_3_1","unstructured":"Fycompa.2017[cited 2018 Mar 18]. 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