{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:58:13Z","timestamp":1792108693145,"version":"4.4.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cenobamate is an antiseizure medication (ASM) approved for the treatment of partial\u2010onset seizures in adults. As both an inductor and an inhibitor of hepatic enzymes, cenobamate affects the metabolism of other ASMs, among which is clobazam. To our knowledge, the extent of interaction between cenobamate and clobazam and its clinical significance have not been studied yet. In this retrospective study we assessed serum concentrations of clobazam and <jats:italic>N<\/jats:italic>\u2010desmethylclobazam (NCLB)in five patients before and after co\u2010medication with cenobamate and calculated the percentage increase in concentration\u2010to\u2010dose ratio (CDR) of both. We were able to demonstrate that the addition of cenobamate resulted in an increase in serum concentration and consequently in CDR of NCLB in all patients. However this occurred in variable degrees: NCLB concentration showed an increase of 1208\u2009\u03bcg\/L (CDR145%) in one patient and between 1691\u2009\u03bc\/L (CDR 819%) and 3995\u2009\u03bc\/L (CDR 1852%) in the other four. This resulted in fatigue, which improved after dose reduction of CLB. Therefore, it is to be concluded that concomitant administration of cenobamate and clobazam can lead to a substantial increase in serum concentrations of NCLB. This can have a positive therapeutic effect on one hand; however, on the other hand, this can lead to unwanted fatigue.<\/jats:p>","DOI":"10.1111\/epi.17515","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T13:39:23Z","timestamp":1674221963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["A retrospective non\u2010interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5008-5864","authenticated-orcid":false,"given":"Sally","family":"Elakkary","sequence":"first","affiliation":[{"name":"Department of Epileptology (Krankenhaus Mara) Bielefeld University  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8158-7442","authenticated-orcid":false,"given":"Anne","family":"Hagemann","sequence":"additional","affiliation":[{"name":"Society for Epilepsy Research  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Klimpel","sequence":"additional","affiliation":[{"name":"MVZ Labor Krone GbR  Bad Salzuflen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-8654","authenticated-orcid":false,"given":"Christian G.","family":"Bien","sequence":"additional","affiliation":[{"name":"Department of Epileptology (Krankenhaus Mara) Bielefeld University  Bielefeld Germany"},{"name":"MVZ Labor Krone GbR  Bad Salzuflen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-1640","authenticated-orcid":false,"given":"Christian","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Epileptology (Krankenhaus Mara) Bielefeld University  Bielefeld Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,26]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"SK Life Science.Xcopri (cenobamate) (package insert). U.S. Food and Drug Administration website.2019.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/212839s000lbl.pdf. Accessed 7 Feb 2023."},{"key":"e_1_2_12_3_1","unstructured":"Angelini Pharma S.p.C.Ontozry (cenobamate) (summary of product characteristics). European Medicines Agency website.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/ontozry\u2010epar\u2010product\u2010information_en.pdf. Accessed 7 Feb 2023."},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30399-0"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173117"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.05.007"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-021-00819-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.769"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S281490"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1979.tb04664.x"},{"issue":"4","key":"e_1_2_12_11_1","first-page":"286","article-title":"Analysis of parent drug\u2010metabolite relationship in the presence of an inducer. Application to the carbamazepine\u2010clobazam interaction in normal man","volume":"11","author":"Levy RH","year":"1983","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.11.1279"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1953"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000327"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32834d4962"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.87"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12830"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.132"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106459"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17515","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17515","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17515","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T19:35:07Z","timestamp":1692732907000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,26]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/epi.17515"],"URL":"https:\/\/doi.org\/10.1111\/epi.17515","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,26]]},"assertion":[{"value":"2022-11-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}