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

Angela K Birnbaum, Ashwin Karanam, Susan E Marino, Christopher M Barkley, Rory P Remmel, Michaela Roslawski, Mary Gramling-Aden, Ilo E Leppik

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1586-1592
Number of pages7
JournalEpilepsia
Volume60
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Cannabidiol
Capsules
Epilepsy
Pharmacokinetics
Food
Seizures
Fasting
Fats
Confidence Intervals
Breakfast
Partial Epilepsy
Cannabis
Biological Availability
Area Under Curve
Meals

Keywords

  • CBD
  • cannabidiol
  • epilepsy
  • food-effect
  • pharmacokinetics

PubMed: MeSH publication types

  • Journal Article

Cite this

Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy. / Birnbaum, Angela K; Karanam, Ashwin; Marino, Susan E; Barkley, Christopher M; Remmel, Rory P; Roslawski, Michaela; Gramling-Aden, Mary; Leppik, Ilo E.

In: Epilepsia, Vol. 60, No. 8, 01.01.2019, p. 1586-1592.

Research output: Contribution to journalArticle

@article{dc476360c3ef48fa8ef73d135dd26349,
title = "Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy",
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",
author = "Birnbaum, {Angela K} and Ashwin Karanam and Marino, {Susan E} and Barkley, {Christopher M} and Remmel, {Rory P} and Michaela Roslawski and Mary Gramling-Aden and Leppik, {Ilo E}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/epi.16093",
language = "English (US)",
volume = "60",
pages = "1586--1592",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy

AU - Birnbaum, Angela K

AU - Karanam, Ashwin

AU - Marino, Susan E

AU - Barkley, Christopher M

AU - Remmel, Rory P

AU - Roslawski, Michaela

AU - Gramling-Aden, Mary

AU - Leppik, Ilo E

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - CBD

KW - cannabidiol

KW - epilepsy

KW - food-effect

KW - pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85068193980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068193980&partnerID=8YFLogxK

U2 - 10.1111/epi.16093

DO - 10.1111/epi.16093

M3 - Article

C2 - 31247132

AN - SCOPUS:85068193980

VL - 60

SP - 1586

EP - 1592

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 8

ER -