Food Effect on Pharmacokinetics of Cannabidiol Oral Capsules in Adult Patients With Refractory Epilepsy

Epilepsia. 2019 Aug;60(8):1586-1592. doi: 10.1111/epi.16093. Epub 2019 Jun 27.

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 (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.

Keywords: CBD; cannabidiol; epilepsy; food-effect; pharmacokinetics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use
  • Cannabidiol / administration & dosage
  • Cannabidiol / blood
  • Cannabidiol / pharmacokinetics*
  • Cannabidiol / therapeutic use
  • Capsules
  • Drug Resistant Epilepsy / drug therapy*
  • Drug Resistant Epilepsy / metabolism
  • Female
  • Food-Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Postprandial Period

Substances

  • Anticonvulsants
  • Capsules
  • Cannabidiol