Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy

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 (AUC_0-∞), and time-to-maximum concentration (T_max) were calculated. The confidence intervals (CIs) for log-transformed C_max and AUC_0-∞ 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 AUC_0-∞ 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for C_max and AUC_0-∞ were 7.47-31.86 and 3.42-7.82, respectively. No sequence or period effect for C_max and AUC_0-∞ 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 AUC_0-∞ and can account for variability in bioavailability and overall drug exposure within patients with oral products.