{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:12:15Z","timestamp":1769098335039,"version":"3.49.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","clinicaltherapeutics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Therapeutics"],"published-print":{"date-parts":[[2017,10]]},"DOI":"10.1016\/j.clinthera.2017.08.020","type":"journal-article","created":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T10:31:11Z","timestamp":1506594671000},"page":"2073-2086","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Thorough QT\/QTc Study of Clobazam in Healthy Volunteers"],"prefix":"10.1016","volume":"39","author":[{"given":"Dwain","family":"Tolbert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Walzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ihor","family":"Bekersky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Reid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.clinthera.2017.08.020_bib1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S1474-4422(08)70292-8","article-title":"Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology","volume":"8","author":"Arzimanoglou","year":"2009","journal-title":"Lancet Neurol"},{"issue":"Suppl 8","key":"10.1016\/j.clinthera.2017.08.020_bib2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1528-1167.2009.02228.x","article-title":"Dravet syndrome: from electroclinical characteristics to molecular biology","volume":"50","author":"Arzimanoglou","year":"2009","journal-title":"Epilepsia"},{"key":"10.1016\/j.clinthera.2017.08.020_bib3","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2165\/11530220-000000000-00000","article-title":"Medical management of Lennox-Gastaut syndrome","volume":"24","author":"Michoulas","year":"2010","journal-title":"CNS Drugs"},{"key":"10.1016\/j.clinthera.2017.08.020_bib4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.eplepsyres.2016.12.011","article-title":"Determining factors of electrocardiographic abnormalities in patients with epilepsy: A case-control study","volume":"129","author":"de Sousa","year":"2017","journal-title":"Epilepsy Res"},{"key":"10.1016\/j.clinthera.2017.08.020_bib5","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1111\/j.1528-1167.2012.03561.x","article-title":"Long-term cardiac rhythm and repolarization abnormalities in refractory focal and generalized epilepsy","volume":"53","author":"Nei","year":"2012","journal-title":"Epilepsia"},{"key":"10.1016\/j.clinthera.2017.08.020_bib6","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/j.1469-8749.2008.03165.x","article-title":"Twenty years after childhood-onset symptomatic generalized epilepsy the social outcome is usually dependency or death: a population-based study","volume":"50","author":"Camfield","year":"2008","journal-title":"Dev Med Child Neurol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib7","series-title":"Onfi (clobazam) [package insert]","year":"2011"},{"key":"10.1016\/j.clinthera.2017.08.020_bib8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/FTD.0b013e31827ada88","article-title":"Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies","volume":"35","author":"de Leon","year":"2013","journal-title":"Ther Drug Monit"},{"key":"10.1016\/j.clinthera.2017.08.020_bib9","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.clinthera.2017.08.020_bib10","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1111\/j.1365-2125.1984.tb02558.x","article-title":"Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients","volume":"18","author":"Jawad","year":"1984","journal-title":"Br J Clin Pharmacol"},{"issue":"Suppl 1","key":"10.1016\/j.clinthera.2017.08.020_bib11","doi-asserted-by":"crossref","first-page":"51S","DOI":"10.1111\/j.1365-2125.1979.tb04665.x","article-title":"Pharmacokinetics of single and multiple doses of clobazam in humans","volume":"7","author":"Rupp","year":"1979","journal-title":"Br J Clin Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib12","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/j.1528-1167.2008.01935.x","article-title":"Clobazam in the treatment of Lennox-Gastaut syndrome","volume":"50","author":"Conry","year":"2009","journal-title":"Epilepsia"},{"key":"10.1016\/j.clinthera.2017.08.020_bib13","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1212\/WNL.0b013e318232de76","article-title":"OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome","volume":"77","author":"Ng","year":"2011","journal-title":"Neurology"},{"key":"10.1016\/j.clinthera.2017.08.020_bib14","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/S0140-6736(99)02107-8","article-title":"Long QT syndromes and torsade de pointes","volume":"354","author":"Viskin","year":"1999","journal-title":"Lancet"},{"key":"10.1016\/j.clinthera.2017.08.020_bib15","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1038\/bjp.2008.238","article-title":"Cellular basis of drug-induced torsades de pointes","volume":"154","author":"Roden","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib16","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1177\/0091270006286436","article-title":"Clinical evaluation of QT\/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs: the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline","volume":"46","author":"Darpo","year":"2006","journal-title":"J Clin Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.0954-6820.1920.tb18266.x","article-title":"The duration of systole in the electrocardiogram of normal subjects and of patients with heart disease","volume":"53","author":"Fridericia","year":"1920","journal-title":"Acta Med Scand"},{"key":"10.1016\/j.clinthera.2017.08.020_bib18","first-page":"353","article-title":"An analysis of time relations in electrocardiograms","volume":"7","author":"Bazett","year":"1920","journal-title":"Heart"},{"key":"10.1016\/j.clinthera.2017.08.020_bib19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/978-3-662-46943-9_17","article-title":"Clinical ECG assessment","volume":"229","author":"Darpo","year":"2015","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib20","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1067\/mcp.2000.111482","article-title":"Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects","volume":"68","author":"Demolis","year":"2000","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.clinthera.2017.08.020_bib21","series-title":"Avelox (moxifloxacin HCl) [package insert]","year":"2016"},{"key":"10.1016\/j.clinthera.2017.08.020_bib22","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-3-540-74806-9_16","article-title":"Midazolam and other benzodiazepines","author":"Olkkola","year":"2008","journal-title":"Handb Exp Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1517\/14656566.3.5.479","article-title":"Psychotropic drugs and the ECG: focus on the QTc interval","volume":"3","author":"Goodnick","year":"2002","journal-title":"Expert Opin Pharmacother"},{"key":"10.1016\/j.clinthera.2017.08.020_bib24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/jat.975","article-title":"QT prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary screening of torsadogenicity of drugs and drug candidates","volume":"24","author":"Testai","year":"2004","journal-title":"J Appl Toxicol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/bcpt.12434","article-title":"Adverse events associated with flumazenil treatment for the management of suspected benzodiazepine intoxication\u2014a systematic review with meta-analyses of randomised trials","volume":"118","author":"Penninga","year":"2016","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1258\/rsmmsl.49.1.65","article-title":"Acute intoxication by triazolam and promazine: a case report","volume":"49","author":"Rossi","year":"2009","journal-title":"Med Sci Law"},{"key":"10.1016\/j.clinthera.2017.08.020_bib27","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1520\/JFS2002323","article-title":"A fatal drug interaction between oxycodone and clonazepam","volume":"48","author":"Burrows","year":"2003","journal-title":"J Forensic Sci"},{"key":"10.1016\/j.clinthera.2017.08.020_bib28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/15563650903524126","article-title":"A case of torsades de pointes induced by severe QT prolongation after an overdose of eperisone and triazolam in a patient receiving nifedipine","volume":"48","author":"Yamagiwa","year":"2010","journal-title":"Clin Toxicol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib29","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/jat\/21.3.218","article-title":"A fatality due to alprazolam intoxication","volume":"21","author":"Jenkins","year":"1997","journal-title":"J Anal Toxicol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib30","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1211\/0022357991772385","article-title":"First-degree atrioventricular block in alprazolam overdose reversed by flumazenil","volume":"51","author":"Mullins","year":"1999","journal-title":"J Pharmacy Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5455\/medarh.2012.66.49-52","article-title":"Benzodiazepines co-ingestion in reducing tricyclic antidepressant toxicity","volume":"66","author":"Eizadi-Mood","year":"2012","journal-title":"Med Arh"},{"key":"10.1016\/j.clinthera.2017.08.020_bib32","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/ADM.0b013e3182a8a4f2","article-title":"Prospective study of QTc changes among former opiate addicts since admission to methadone maintenance treatment: benzodiazepine risk","volume":"7","author":"Peles","year":"2013","journal-title":"J Addiction Med"},{"key":"10.1016\/j.clinthera.2017.08.020_bib33","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/FJC.0b013e3181f1d21b","article-title":"Increased cardiac risk in concomitant methadone and diazepam treatment: pharmacodynamic interactions in cardiac ion channels","volume":"56","author":"Kuryshev","year":"2010","journal-title":"J Cardiovasc Pharmacol"},{"key":"10.1016\/j.clinthera.2017.08.020_bib34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.yebeh.2014.05.016","article-title":"Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome","volume":"37","author":"Tolbert","year":"2014","journal-title":"Epilepsy Behav"},{"key":"10.1016\/j.clinthera.2017.08.020_bib35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.31887\/DCNS.2008.10.1\/hcrgrunze","article-title":"The effectiveness of anticonvulsants in psychiatric disorders","volume":"10","author":"Grunze","year":"2008","journal-title":"Dialogues Clin Neurosci"},{"key":"10.1016\/j.clinthera.2017.08.020_bib36","series-title":"Benzodiazepines in Older Adults: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines","author":"McIntosh","year":"2011"},{"key":"10.1016\/j.clinthera.2017.08.020_bib37","unstructured":"E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs\u2014Questions and Answers (R1). https:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/ucm323656.htm. Accessed April 20, 2017."}],"container-title":["Clinical Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149291817309414?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149291817309414?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T16:26:12Z","timestamp":1659543972000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0149291817309414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["S0149291817309414"],"URL":"https:\/\/doi.org\/10.1016\/j.clinthera.2017.08.020","relation":{},"ISSN":["0149-2918"],"issn-type":[{"value":"0149-2918","type":"print"}],"subject":[],"published":{"date-parts":[[2017,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Thorough QT\/QTc Study of Clobazam in Healthy Volunteers","name":"articletitle","label":"Article Title"},{"value":"Clinical Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clinthera.2017.08.020","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}