{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:28:22Z","timestamp":1792517302242,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T00:00:00Z","timestamp":1550707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"GW Research Ltd"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    GW Pharmaceuticals\u2019 formulation of highly purified cannabidiol oral solution is approved in the United States for seizures associated with Lennox\u2010Gastaut and Dravet syndromes in patients aged \u22652 years, for which clobazam, stiripentol, and valproate are commonly used antiepileptic drugs. This open\u2010label, fixed\u2010sequence, drug\u2010drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady\u2010state pharmacokinetics of clobazam (and N\u2010desmethylclobazam), stiripentol, and valproate; the reciprocal effect of clobazam, stiripentol, and valproate on cannabidiol and its major metabolites (7\u2010hydroxy\u2010cannabidiol [7\u2010OH\u2010CBD] and 7\u2010carboxy\u2010cannabidiol [7\u2010COOH\u2010CBD]); and cannabidiol safety and tolerability when coadministered with each antiepileptic drug. Concomitant cannabidiol had little effect on clobazam exposure (maximum concentration [C\n                    <jats:sub>max<\/jats:sub>\n                    ] and area under the concentration\u2010time curve [AUC], 1.2\u2010fold), N\u2010desmethylclobazam exposure increased (C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC, 3.4\u2010fold), stiripentol exposure increased slightly (C\n                    <jats:sub>max<\/jats:sub>\n                    , 1.3\u2010fold; AUC, 1.6\u2010fold), while no clinically relevant effect on valproate exposure was observed. Concomitant clobazam with cannabidiol increased 7\u2010OH\u2010CBD exposure (C\n                    <jats:sub>max<\/jats:sub>\n                    , 1.7\u2010fold; AUC, 1.5\u2010fold), without notable 7\u2010COOH\u2010CBD or cannabidiol increases. Stiripentol decreased 7\u2010OH\u2010CBD exposure by 29% and 7\u2010COOH\u2010CBD exposure by 13%. There was no effect of valproate on cannabidiol or its metabolites. Cannabidiol was moderately well tolerated, with similar incidences of adverse events reported when coadministered with clobazam, stiripentol, or valproate. There were no deaths, serious adverse events, pregnancies, or other clinically significant safety findings.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.665","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T13:49:46Z","timestamp":1550756986000},"page":"1009-1031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":184,"title":["A Phase 1, Open\u2010Label, Pharmacokinetic Trial to Investigate Possible Drug\u2010Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects"],"prefix":"10.1002","volume":"8","author":[{"given":"Gilmour","family":"Morrison","sequence":"first","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Crockett","sequence":"additional","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Blakey","sequence":"additional","affiliation":[{"name":"consult2deliver  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Sommerville","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences, Inc.  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