{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:44:11Z","timestamp":1792071851878,"version":"4.4.0"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cenobamate is a new antiseizure medication with an unusually high seizure\u2010free rate, resulting in frequent use in patients with drug\u2010resistant epilepsy. Many of these patients are taking clobazam (CLB) at baseline. Cenobamate has important interactions with CLB, requiring CLB dose adjustment in conjunction with cenobamate titration. There is limited guidance on the optimal CLB dose adjustment after cenobamate introduction and titration. We measured levels of CLB and its active metabolite N\u2010desmethylclobazam (N\u2010CLB) before and after cenobamate titration in 10 subjects with drug\u2010resistant focal epilepsy. The mean CLB dose at baseline was 34.5\u2009mg\/day (range\u2009=\u200915\u201360\u2009mg\/day). We empirically started reducing the dose of CLB when starting 25\u2009mg of cenobamate, then we cut the CLB dose down to 10 or 5\u2009mg when reaching a cenobamate dose of 50\u2009mg daily. The mean final dose of CLB was 9\u2009mg (74% reduction). The average combined CLB\u2009+\u2009N\u2010CLB level after cenobamate titration was 2191 \u03bcg\/mL, not significantly different from baseline (2358 \u03bcg\/mL). Although there may be individual variability, a 70%\u201374% CLB dose reduction may be appropriate to achieve an equivalent combined CLB\u2009+\u2009N\u2010CLB level.<\/jats:p>","DOI":"10.1002\/epi.70437","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:45:25Z","timestamp":1792068325000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Change in clobazam pharmacokinetics after introduction of cenobamate"],"prefix":"10.1002","author":[{"given":"Melissa R.","family":"Osborn","sequence":"first","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin F.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6559-1329","authenticated-orcid":false,"given":"Bassel W.","family":"Abou\u2010Khalil","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/jcph.1313","article-title":"A comprehensive overview of the clinical pharmacokinetics of Clobazam","volume":"59","author":"Tolbert D","year":"2019","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s40263-021-00819-8","article-title":"Pharmacology of Cenobamate: mechanism of action, pharmacokinetics, drug\u2010drug interactions and tolerability","volume":"35","author":"Roberti R","year":"2021","journal-title":"CNS Drugs"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.yebeh.2023.109156","article-title":"The cenobamate\u2010clobazam interaction\u2010 evidence of synergy in addition to pharmacokinetic interaction","volume":"142","author":"Osborn M","year":"2023","journal-title":"Epilepsy Behav"},{"issue":"94","key":"e_1_2_11_5_1","first-page":"e2311","article-title":"Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures","volume":"2","author":"Chung SS","year":"2020","journal-title":"Neurology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1474-4422(19)30399-0","article-title":"Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double\u2010blind, randomised, placebo\u2010controlled, dose\u2010response trial","volume":"19","author":"Krauss GL","year":"2020","journal-title":"Lancet Neurol"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1002\/epi.70184","article-title":"Pharmacokinetic variability and complex two\u2010way interactions with cenobamate in patients with refractory epilepsy","volume":"67","author":"Johannessen Landmark C","year":"2026","journal-title":"Epilepsia"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10072-026-09048-7","article-title":"Early sedation\u2010related adverse events with the cenobamate\u2010clobazam combination in drug\u2010resistant epilepsy: real\u2010world preliminary observations","volume":"47","author":"Falcicchio G","year":"2026","journal-title":"Neurol Sci"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1111\/epi.17515","article-title":"A retrospective non\u2010interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam","volume":"64","author":"Elakkary S","year":"2023","journal-title":"Epilepsia"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.yebeh.2025.110835","article-title":"Quality of life and synergistic combinations of antiseizure medication in patients treated with cenobamate in early therapy lines for focal\u2010onset seizures","volume":"175","author":"Winter Y","year":"2026","journal-title":"Epilepsy Behav"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1002\/epi4.70261","article-title":"Effectiveness of adjunctive low\u2010dose clobazam in adults with focal drug\u2010resistant epilepsy and incomplete response to cenobamate: a real\u2010world study","volume":"11","author":"Ciullo I","year":"2026","journal-title":"Epilepsia Open"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.2042-7158.1984.tb04917.x","article-title":"Plasma concentrations of clobazam and its N\u2010desmethyl metabolite; protection against pentetrazol\u2010induced convulsions in mice","volume":"36","author":"Haigh JR","year":"1984","journal-title":"J Pharm Pharmacol"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/j.1528-1157.1996.tb00643.x","article-title":"Effects of clobazam and its active metabolite on GABA\u2010activated currents in rat cerebral neurons in culture","volume":"37","author":"Nakamura F","year":"1996","journal-title":"Epilepsia"},{"issue":"1","key":"e_1_2_11_14_1","first-page":"7S","article-title":"Pharmacology of anti\u2010anxiety drugs with special reference to clobazam","volume":"7","author":"Fielding S","year":"1979","journal-title":"Br J Clin Pharmacol"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1111\/epi.18091","article-title":"Adjunctive cenobamate in people with focal onset seizures: insights from the Italian expanded access program","volume":"65","author":"Roberti R","year":"2024","journal-title":"Epilepsia"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70437","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70437","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:45:27Z","timestamp":1792068327000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":14,"alternative-id":["10.1002\/epi.70437"],"URL":"https:\/\/doi.org\/10.1002\/epi.70437","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"assertion":[{"value":"2026-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"epi.70437"}}