Abstract
Objective
To evaluate the pharmacokinetics of a purified oral cannabidiol (CBD) capsule administered with and without food in adults with refractory epilepsy.
Methods
Adult patients who were prescribed CBD for seizures, had localization‐related intractable epilepsy with ≥4 seizures per month, and qualified for Minnesota cannabis were enrolled. A single dose of 99% pure CBD capsules was taken under both fasting (no breakfast) and fed (high fat 840‐860 calorie) conditions. Blood sampling for CBD plasma concentrations was performed under each condition between 0 and 72 hours post‐dose and measured by a validated liquid chormatography‐mass spectometry assay. CBD pharmacokinetic profiles including maximum concentration (C
max), area‐under‐the‐curve from zero to infinity (AUC0‐∞), and time‐to‐maximum concentration (T
max) were calculated. The confidence intervals (CIs) for log‐transformed C
max and AUC0‐∞ ratios between fed and fasting states were calculated. Seizure and adverse events information was collected.
Results
Eight patients completed the study. On average C
max was 14 times and AUC0‐∞ 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for C
max and AUC0‐∞ were 7.47‐31.86 and 3.42‐7.82, respectively. No sequence or period effect for C
max and AUC0‐∞ was observed. No adverse events were reported.
Significance
Administering CBD as a capsule rather than a liquid allows for more precise determination of pharmacokinetics parameters and is more representative of CBD swallowed products. The fat content of a meal can lead to significant increases in C
max and AUC0‐∞ and can account for variability in bioavailability and overall drug exposure within patients with oral products.
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