{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:36Z","timestamp":1791859056075,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>When highly purified cannabidiol (CBD; Epidiolex) and the mammalian target of rapamycin inhibitor everolimus are used concomitantly in the treatment of tuberous sclerosis complex, there is evidence of a pharmacokinetic (PK) interaction, leading to increased everolimus systemic exposure. We evaluated the effect of steady\u2010state CBD exposure following multiple clinically relevant CBD doses on everolimus PK in healthy adult participants in a single\u2010center, fixed\u2010sequence, open\u2010label, phase 1 study. All participants received oral everolimus 5\u00a0mg on day 1, followed by a 7\u2010day washout. On days 9\u201317, participants received CBD (100\u00a0mg\/mL oral solution) at 12.5\u00a0mg\/kg in the morning and evening. On the morning of day 13, participants also received a single dose of oral everolimus 5\u00a0mg. Medications were taken 30 or 45\u00a0minutes (morning or evening dose) after starting a standardized meal. Maximum concentration and area under the concentration\u2010time curve (AUC) from time of dosing to the last measurable concentration and extrapolated to infinity, of everolimus in whole blood were estimated using noncompartmental analysis, with geometric mean ratios and 90% confidence intervals for the ratios of everolimus dosed with CBD to everolimus dosed alone. A single dose of everolimus 5\u00a0mg was well tolerated when administered with multiple doses of CBD. Log\u2010transformed everolimus maximum concentration, AUC from time of dosing to the last measurable concentration, and AUC extrapolated to infinity values increased by \u22482.5\u2010fold, and everolimus half\u2010life remained largely unchanged in the presence of steady\u2010state CBD relative to everolimus dosed alone. Everolimus blood concentration monitoring should be strongly advised with appropriate dose reduction when coadministered with CBD.<\/jats:p>","DOI":"10.1002\/cpdd.1262","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T09:06:39Z","timestamp":1683104799000},"page":"911-919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Pharmacokinetic Drug\u2010Drug Interaction With Coadministration of Cannabidiol and Everolimus in a Phase 1 Healthy Volunteer Trial"],"prefix":"10.1002","volume":"12","author":[{"given":"Louise","family":"Wray","sequence":"first","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Berwaerts","sequence":"additional","affiliation":[{"name":"Greenwich Biosciences Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Critchley","sequence":"additional","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Hyland","sequence":"additional","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Chen","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching","family":"Thai","sequence":"additional","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bola","family":"Tayo","sequence":"additional","affiliation":[{"name":"GW Research Ltd  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1708349"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4607"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61767-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31419-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001671"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1695786"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa222.041"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443020-00002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.00032"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.02.017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02434.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005275368"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000294"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01365"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26123573"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2512"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16674"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000350"},{"key":"e_1_2_9_21_1","unstructured":"WhalleyB StottC GrayR JonesN.The human metabolite of cannabidiol 7\u2010hydroxy cannabidiol but not 7\u2010carboxy cannabidiol is anticonvulsant in the maximal electroshock seizure threshold test (MEST) in mouse. American Epilepsy Society Meeting Abstract 1.435;2017."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.950"},{"key":"e_1_2_9_23_1","first-page":"11","article-title":"Bioavailability of everolimus administered as a single 5\u00a0mg tablet versus five 1\u00a0mg tablets: a randomized, open\u2010label, two\u2010way crossover study of healthy volunteers","volume":"7","author":"Thudium K","year":"2015","journal-title":"Clin Pharmacol"},{"key":"e_1_2_9_24_1","unstructured":"MorrisonG TaylorL CrockettJ CritchleyD TayoB.A phase 1 investigation into the potential effects of cannabidiol on CYP3A4\u2010mediated drug\u2010drug interactions in healthy volunteers. 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