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-infinity)), and time-to-maximum concentration (T-max) were calculated. The confidence intervals (CIs) for log-transformed C-max and AUC(0-infinity) 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-infinity) 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for C-max and AUC(0-infinity) were 7.47-31.86 and 3.42-7.82, respectively. No sequence or period effect for C-max and AUC(0-infinity) 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-infinity) and can account for variability in bioavailability and overall drug exposure within patients with oral products.