Background and Objectives
Despite limited evidence, cannabidiol-rich cannabis extracts have been popularly used in pediatrics. With increased use, it is critical to determine basic pharmacokinetic parameters of cannabidiol in these extracts in the pediatric population. The objective of this study was to determine the disposition of oral cannabidiol cannabis extracts and drug interactions in children with pediatric epilepsy.
We conducted a prospective observational study evaluating the disposition of oral cannabidiol in children (< 18 years of age) receiving cannabidiol extracts for epilepsy. Subjects underwent serial blood draws after oral cannabidiol administration. Cannabidiol and metabolites, along with anticonvulsant concentrations were determined.
Twenty-nine patients had sufficient pharmacokinetic data and were included in the analysis. Mean age was 9.7 years (standard deviation 4.3) and 17 patients (59%) were male. Median peak plasma cannabidiol concentrations was 13.1 ng/mL (interquartile range 6.8–39.3 ng mL); median time to peak of 2.0 h (interquartile range 2.0–4.0 h). Mean acute elimination half-life of oral cannabidiol was 6.2 h (standard deviation 1.8 h). There was an observed half-life of degradation of 533 days noted for cannabidiol concentrations when stored for 0.6–3.1 years. There was some impact on cannabidiol pharmacokinetic parameters when cannabidiol was co-administered with zonisamide (elimination rate constant and V1) and levetiracetam (elimination rate constant).
In pediatric patients using oral cannabidiol-rich cannabis extract for epilepsy, the time to peak concentration of plasma cannabidiol and average acute elimination half-life were shorter than those reported for adults. Co-administration of zonisamide and levetiracetam had some impact on cannabidiol pharmacokinetic parameters. There was an observed degradation of plasma cannabidiol in long-term storage.
ClinicalTrials.gov Identifer no. NCT02447198.
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This work was supported by the Colorado Department of Public Health and Environment Medical Marijuana Grant Program (18-103031, to George Sam Wang, David W.A. Bourne, Jost Klawitter, Cristina Sempio, Uwe Christians, Kevin Chapman, Kelly Knupp, Laura Borgelt, Michael F. Wempe, and Lalit Bajaj). George Sam Wang has received royalties from UpToDate, and is a co-investigator on grant NIH1R01DA045051-01A1 on related subjects. Laura Borgelt has received funding for research from the Colorado Department of Public Health and Environment and honoraria for providing continuing education from PharmCon, Inc. on related subjects. Kelly Knupp was a consultant for GW pharmaceuticals and participated in drug safety and monitoring board.
Conflict of interest
George Sam Wang, David W. A. Bourne, Jost Klawitter, Cristina Sempio, Kevin Chapman, Kelly Knupp, Michael F. Wempe, Laura Borgelt, Uwe Christians, Jan Leonard, Kennon Heard, and Lalit Bajaj have no conflicts of interest that are directly relevant to the content of this article.
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Wang, G.S., Bourne, D.W.A., Klawitter, J. et al. Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy. Clin Pharmacokinet (2020). https://doi.org/10.1007/s40262-020-00869-z