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

• Published in: Epilepsia (Copenhagen) Vol. 60; no. 8; pp. 1586 - 1592
• Main Authors: Birnbaum, Angela K., Karanam, Ashwin, Marino, Susan E., Barkley, Christopher M., Remmel, Rory P., Roslawski, Michaela, Gramling‐Aden, Mary, Leppik, Ilo E.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-08-2019
• Subjects: Administration, Oral; Adult; Aged; Anticonvulsants - administration & dosage; Anticonvulsants - blood; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Bioavailability; cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - blood; Cannabidiol - pharmacokinetics; Cannabidiol - therapeutic use; Cannabinoids; Cannabis; Capsules; CBD; Convulsions & seizures; Drug Resistant Epilepsy - drug therapy; Drug Resistant Epilepsy - metabolism; Epilepsy; Fasting; Female; Food-Drug Interactions; food‐effect; Humans; Localization; Male; Middle Aged; Pharmacokinetics; Postprandial Period; Seizures; cannabidiol; epilepsy; food-effect; pharmacokinetics; CBD
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/epi.16093

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 (Cmax), area‐under‐the‐curve from zero to infinity (AUC0‐∞), and time‐to‐maximum concentration (Tmax) were calculated. The confidence intervals (CIs) for log‐transformed Cmax 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 Cmax was 14 times and AUC0‐∞ 4 times higher in the fed state. The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0‐∞ were 7.47‐31.86 and 3.42‐7.82, respectively. No sequence or period effect for Cmax 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 Cmax and AUC0‐∞ and can account for variability in bioavailability and overall drug exposure within patients with oral products.