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

Autor: Birnbaum AK; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Karanam A; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Marino SE; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Barkley CM; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Remmel RP; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Roslawski M; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Gramling-Aden M; MINCEP Epilepsy Care, University of Minnesota Physicians, Minneapolis, Minnesota., Leppik IE; Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; Center for Clinical and Cognitive Neuropharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.; MINCEP Epilepsy Care, University of Minnesota Physicians, Minneapolis, Minnesota.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2019 Aug; Vol. 60 (8), pp. 1586-1592. Date of Electronic Publication: 2019 Jun 27.
DOI: 10.1111/epi.16093
Abstrakt: 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.
(Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)
Databáze: MEDLINE
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