{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:22:24Z","timestamp":1787167344701,"version":"build-2736575974"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100011944","name":"School of Public Health, University of California Berkeley","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011944","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009655","name":"Sunovion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","epilepsybehavior.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Epilepsy &amp; Behavior"],"published-print":{"date-parts":[[2019,10]]},"DOI":"10.1016\/j.yebeh.2019.106459","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T17:27:31Z","timestamp":1568136451000},"page":"106459","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":37,"special_numbering":"C","title":["Drug\u2013drug interactions and pharmacodynamics of concomitant clobazam and cannabidiol or stiripentol in refractory seizures"],"prefix":"10.1016","volume":"99","author":[{"given":"Pavel","family":"Klein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwain","family":"Tolbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Gidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yebeh.2019.106459_bb0005","series-title":"Full prescribing information","author":"Onfi (clobazam)","year":"2016"},{"key":"10.1016\/j.yebeh.2019.106459_bb0010","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1017\/cjn.2016.249","article-title":"Treatment of Dravet syndrome","volume":"43","author":"Wirrell","year":"2016","journal-title":"Can J Neurol Sci"},{"key":"10.1016\/j.yebeh.2019.106459_bb0015","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1528-1167.2011.03178.x","article-title":"Rational approach to treatment options for Lennox-Gastaut syndrome","volume":"52","author":"Montouris","year":"2011","journal-title":"Epilepsia"},{"key":"10.1016\/j.yebeh.2019.106459_bb0020","series-title":"Full prescribing information","author":"Epidiolex (cannabidiol)","year":"2018"},{"key":"10.1016\/j.yebeh.2019.106459_bb0025","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/S1474-4422(15)00379-8","article-title":"Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial","volume":"15","author":"Devinsky","year":"2016","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0030","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N Engl J Med"},{"key":"10.1016\/j.yebeh.2019.106459_bb0035","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1714631","article-title":"Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome","volume":"378","author":"Devinsky","year":"2018","journal-title":"N Engl J Med"},{"key":"10.1016\/j.yebeh.2019.106459_bb0040","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(18)30136-3","article-title":"Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial","volume":"391","author":"Thiele","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.yebeh.2019.106459_bb0045","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1111\/epi.13060","article-title":"Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy","volume":"56","author":"Geffrey","year":"2015","journal-title":"Epilepsia"},{"key":"10.1016\/j.yebeh.2019.106459_bb0050","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1124\/dmd.32.11.1279","article-title":"In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19","volume":"32","author":"Giraud","year":"2004","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.yebeh.2019.106459_bb0055","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0060","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2133\/dmpk.DMPK-12-RG-129","article-title":"Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19","volume":"28","author":"Jiang","year":"2013","journal-title":"Drug Metab Pharmacokinet"},{"key":"10.1016\/j.yebeh.2019.106459_bb0065","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.lfs.2011.02.017","article-title":"Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety","volume":"88","author":"Yamaori","year":"2011","journal-title":"Life Sci"},{"key":"10.1016\/j.yebeh.2019.106459_bb0070","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1124\/dmd.111.041384","article-title":"Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6","volume":"39","author":"Yamaori","year":"2011","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.yebeh.2019.106459_bb0075","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1111\/epi.13852","article-title":"Interactions between cannabidiol and commonly used antiepileptic drugs","volume":"58","author":"Gaston","year":"2017","journal-title":"Epilepsia"},{"key":"10.1016\/j.yebeh.2019.106459_bb0080","doi-asserted-by":"crossref","first-page":"e1204-e11","DOI":"10.1212\/WNL.0000000000005254","article-title":"Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome","volume":"90","author":"Devinsky","year":"2018","journal-title":"Neurology"},{"key":"10.1016\/j.yebeh.2019.106459_bb0085","doi-asserted-by":"crossref","DOI":"10.1002\/cpdd.665","article-title":"A phase 1, open-label, pharmacokinetic trial to investigate possible drug-drug interactions between clobazam, stiripentol, or valproate and cannabidiol in healthy subjects","author":"Morrison","year":"2019","journal-title":"Clin Pharmacol Drug Dev"},{"key":"10.1016\/j.yebeh.2019.106459_bb0090","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1056\/NEJMra1407304","article-title":"Cannabinoids in the treatment of epilepsy","volume":"373","author":"Friedman","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.yebeh.2019.106459_bb0095","author":"Canadian Agency for Drugs and Technologies in Health"},{"key":"10.1016\/j.yebeh.2019.106459_bb0100","author":"European Medicines Agency"},{"key":"10.1016\/j.yebeh.2019.106459_bb0105","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/S0140-6736(00)03157-3","article-title":"Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group","volume":"356","author":"Chiron","year":"2000","journal-title":"Lancet"},{"key":"10.1016\/j.yebeh.2019.106459_bb0110","series-title":"Full prescribing information","author":"Diacomit (stiripentol)","year":"2018"},{"key":"10.1016\/j.yebeh.2019.106459_bb0115","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S0090-9556(25)08990-1","article-title":"The metabolic fate of stiripentol in man","volume":"14","author":"Moreland","year":"1986","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.yebeh.2019.106459_bb0120","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.eplepsyres.2014.03.009","article-title":"Reassessment of stiripentol pharmacokinetics in healthy adult volunteers","volume":"108","author":"Peigne","year":"2014","journal-title":"Epilepsy Res"},{"key":"10.1016\/j.yebeh.2019.106459_bb0125","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1517\/13543784.14.7.905","article-title":"Stiripentol","volume":"14","author":"Chiron","year":"2005","journal-title":"Expert Opin Investig Drugs"},{"key":"10.1016\/j.yebeh.2019.106459_bb0130","series-title":"Presented at: American Academy of Neurology Annual Meeting","article-title":"Pharmacometrics of clobazam in pediatrics: population PK modeling to predict effective clobazam doses for Dravet syndrome","author":"Tolbert","year":"2018"},{"key":"10.1016\/j.yebeh.2019.106459_bb0135","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1212\/WNL.0b013e318232de76","article-title":"Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome","volume":"77","author":"Ng","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.yebeh.2019.106459_bb0140","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/jcph.603","article-title":"Drug-metabolism mechanism: knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions","volume":"56","author":"Tolbert","year":"2016","journal-title":"J Clin Pharmacol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0145","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2125.1987.tb03032.x","article-title":"N-desmethylclobazam: a possible alternative to clobazam in the treatment of refractory epilepsy?","volume":"23","author":"Haigh","year":"1987","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0150","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0163-7258(82)90051-1","article-title":"Kinetics of pharmacologic response","volume":"16","author":"Holford","year":"1982","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.yebeh.2019.106459_bb0155","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/aje\/kwt245","article-title":"Maximum likelihood, profile likelihood, and penalized likelihood: a primer","volume":"179","author":"Cole","year":"2014","journal-title":"Am J Epidemiol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0160","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0088456","article-title":"Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for alpha(2)- versus alpha(1)-GABA(A)-receptor complexes","volume":"9","author":"Jensen","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.yebeh.2019.106459_bb0165","series-title":"Full prescribing information","author":"Depakene (valproic acid)","year":"2011"},{"key":"10.1016\/j.yebeh.2019.106459_bb0170","series-title":"Full prescribing information","author":"Lamictal (lamotrigine)","year":"2015"},{"key":"10.1016\/j.yebeh.2019.106459_bb0175","series-title":"Full prescribing information","author":"Keppra (levetiracetam)","year":"2009"},{"key":"10.1016\/j.yebeh.2019.106459_bb0180","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1097\/00007691-200212000-00009","article-title":"Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam","volume":"24","author":"Contin","year":"2002","journal-title":"Ther Drug Monit"},{"key":"10.1016\/j.yebeh.2019.106459_bb0185","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00228-014-1773-z","article-title":"Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy","volume":"71","author":"Hashi","year":"2015","journal-title":"Eur J Clin Pharmacol"},{"key":"10.1016\/j.yebeh.2019.106459_bb0190","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1124\/dmd.105.007237","article-title":"In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism","volume":"34","author":"Giraud","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1016\/j.yebeh.2019.106459_bb0195","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/FTD.0b013e318283b49a","article-title":"Influence of CYP2C19 polymorphism and concomitant antiepileptic drugs on serum clobazam and N-desmethyl clobazam concentrations in patients with epilepsy","volume":"35","author":"Yamamoto","year":"2013","journal-title":"Ther Drug Monit"},{"key":"10.1016\/j.yebeh.2019.106459_bb0200","author":"US Department of Health and Human Services, US Food and Drug Administration"}],"container-title":["Epilepsy &amp; Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525505019304494?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525505019304494?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:28:37Z","timestamp":1761503317000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525505019304494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":40,"alternative-id":["S1525505019304494"],"URL":"https:\/\/doi.org\/10.1016\/j.yebeh.2019.106459","relation":{},"ISSN":["1525-5050"],"issn-type":[{"value":"1525-5050","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Drug\u2013drug interactions and pharmacodynamics of concomitant clobazam and cannabidiol or stiripentol in refractory seizures","name":"articletitle","label":"Article Title"},{"value":"Epilepsy & Behavior","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yebeh.2019.106459","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"106459"}}