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A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam

We investigated the effects of cannabidiol (CBD; 21‐day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evalua...

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Autores principales: VanLandingham, Kevan E., Crockett, Julie, Taylor, Lesley, Morrison, Gilmour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540496/
https://www.ncbi.nlm.nih.gov/pubmed/32652616
http://dx.doi.org/10.1002/jcph.1634
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author VanLandingham, Kevan E.
Crockett, Julie
Taylor, Lesley
Morrison, Gilmour
author_facet VanLandingham, Kevan E.
Crockett, Julie
Taylor, Lesley
Morrison, Gilmour
author_sort VanLandingham, Kevan E.
collection PubMed
description We investigated the effects of cannabidiol (CBD; 21‐day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite N‐desmethylclobazam (N‐CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant‐derived highly purified CBD (Epidiolex in the United States; 100 mg/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug‐drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day 33:day 1 CLB was 1.0 (90%CI, 0.8‐1.2) for C(max) and 1.1 (90%CI, 0.9‐1.2) for AUC(tau). There was a significant DDI between CBD and N‐CLB: the GMR of day 33:day 1 N‐CLB was 2.2 (90%CI, 1.4‐3.5) for C(max) and 2.6 (90%CI, 2.0‐3.6) for AUC(tau). Placebo had no effect on CLB or N‐CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20 mg/kg/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N‐CLB. The safety profile of GW Pharmaceuticals’ CBD formulation with CLB was consistent with other GW‐sponsored trials.
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spelling pubmed-75404962020-10-09 A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam VanLandingham, Kevan E. Crockett, Julie Taylor, Lesley Morrison, Gilmour J Clin Pharmacol NON COVID ARTICLES We investigated the effects of cannabidiol (CBD; 21‐day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20 patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite N‐desmethylclobazam (N‐CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant‐derived highly purified CBD (Epidiolex in the United States; 100 mg/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug‐drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day 33:day 1 CLB was 1.0 (90%CI, 0.8‐1.2) for C(max) and 1.1 (90%CI, 0.9‐1.2) for AUC(tau). There was a significant DDI between CBD and N‐CLB: the GMR of day 33:day 1 N‐CLB was 2.2 (90%CI, 1.4‐3.5) for C(max) and 2.6 (90%CI, 2.0‐3.6) for AUC(tau). Placebo had no effect on CLB or N‐CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20 mg/kg/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N‐CLB. The safety profile of GW Pharmaceuticals’ CBD formulation with CLB was consistent with other GW‐sponsored trials. John Wiley and Sons Inc. 2020-07-11 2020-10 /pmc/articles/PMC7540496/ /pubmed/32652616 http://dx.doi.org/10.1002/jcph.1634 Text en © 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle NON COVID ARTICLES
VanLandingham, Kevan E.
Crockett, Julie
Taylor, Lesley
Morrison, Gilmour
A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title_full A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title_fullStr A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title_full_unstemmed A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title_short A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
title_sort phase 2, double‐blind, placebo‐controlled trial to investigate potential drug‐drug interactions between cannabidiol and clobazam
topic NON COVID ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540496/
https://www.ncbi.nlm.nih.gov/pubmed/32652616
http://dx.doi.org/10.1002/jcph.1634
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