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To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV\u20101012 (NCT00518713) and 18 healthy participants in bioavailability study OV\u20101017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of clobazam and its metabolite,<jats:italic>N<\/jats:italic>\u2010desmethylclobazam (N\u2010CLB): CYP3A inducers (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate, oxcarbazepine). CYP3A4 inducers\u2014which did not affect the oral clearance of clobazam\u2014significantly increased the formation of N\u2010CLB by 9.4%, while CYP2C19 inducers significantly increased the apparent elimination rate of N\u2010CLB by 10.5%, resulting in a negligible net change in the PK of the active metabolite. CYP2C19 inhibitors did not affect N\u2010CLB elimination. Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.603","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T10:31:03Z","timestamp":1438252263000},"page":"365-374","source":"Crossref","is-referenced-by-count":16,"title":["Drug\u2010metabolism mechanism: Knowledge\u2013based population pharmacokinetic approach for characterizing clobazam drug\u2010drug interactions"],"prefix":"10.1002","volume":"56","author":[{"given":"Dwain","family":"Tolbert","sequence":"first","affiliation":[{"name":"Lundbeck LLC Deerfield IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihor","family":"Bekersky","sequence":"additional","affiliation":[{"name":"Lundbeck LLC Deerfield IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010May","family":"Chu","sequence":"additional","affiliation":[{"name":"Anoixis Corporation Natick MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ene I.","family":"Ette","sequence":"additional","affiliation":[{"name":"Anoixis Corporation Natick MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,29]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"2011 Lundbeck LLC Deerfield IL"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/11599020-000000000-00000"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088456"},{"issue":"11","key":"e_1_2_8_5_1","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 CYP2 C19","volume":"32","author":"Giraud C","year":"2004","journal-title":"Drug Metab Dispos."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1979.tb04664.x"},{"key":"e_1_2_8_7_1","first-page":"1081","article-title":"Effect of renal impairment on pharmacokinetics of clobazam","volume":"50","author":"Walzer MA","year":"2010","journal-title":"J Clin Pharmacol."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.2012.01028.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1990.tb00799.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00544031"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1987.tb03051.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199208000-00002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389701200311"},{"key":"e_1_2_8_14_1","first-page":"155","article-title":"The effects of clobazam on the blood levels of sodium valproate. 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