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Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop‐seizure frequency
Author(s) -
Bergmann Kirsten Riber,
Broekhuizen Karen,
Groeneveld Geert Jan
Publication year - 2020
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14158
Subject(s) - clobazam , cannabidiol , lennox–gastaut syndrome , dravet syndrome , placebo , medicine , anesthesia , epilepsy , pharmacology , cannabis , psychiatry , pathology , alternative medicine
With this study, we aim to test the hypothesis that the effect of cannabidiol on drop‐seizure frequency in patients with Lennox–Gastaut syndrome and Dravet syndrome could be attributed to a drug–drug interaction with clobazam. We performed clinical trial simulations for the effect of 20 mg/kg/day cannabidiol on drop‐seizure frequency in patients with Lennox–Gastaut syndrome. We assumed that patients taking 10 or 20 mg clobazam would have a 2‐ to 7‐fold increase in N‐desmethylclobazam exposure, whereas patients not taking clobazam would have a median reduction in drop‐seizure frequency and a variability in the percent reduction similar to the placebo group. The results show that the effect of cannabidiol on the median reduction in drop‐seizure frequency in patients with Lennox–Gastaut syndrome may be explained by a drug–drug interaction with clobazam. This may have important implications for the use of cannabidiol and its Food and Drug Administration registration.