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Population pharmacokinetics of oral-based administration of cannabidiol in healthy adults: implications for drug development

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dc.contributor.authorSchultz, H.B.
dc.contributor.authorHosseini, A.
dc.contributor.authorMcLachlan, A.J.
dc.contributor.authorReuter, S.E.
dc.date.issued2023
dc.descriptionData source: Supplementary Material, http://doi.org/10.1089/can.2021.0202
dc.description.abstractBackground and Objectives: Cannabidiol (CBD) is increasingly being studied as a therapeutic option for a range of health conditions; however, the pharmacokinetics of CBD is not well understood. This study characterized CBD pharmacokinetics in healthy adults using a population pharmacokinetic approach, informing drug development of oral-based dose forms of CBD. Materials and Methods: CBD concentration-time data were obtained from a phase I, randomized, open-label, four-way crossover study (n=12) and modeled using Phoenix NLME. Monte Carlo simulations were conducted to estimate CBD exposure with chronic dosing as intended for clinical use (50 mg b.i.d.). Results: A three-compartment pharmacokinetic model with a chain of absorption transit compartments and first-order elimination most adequately described CBD pharmacokinetics. Substantial variability in population pharmacokinetic parameters was identified (up to 60%CV), which could not be accounted for by any covariates. Simulations indicated a 3.6-fold difference in drug exposure at steady state with multiple dosing (AUCτ 95% prediction interval: 65.5–138 ng·h/mL), and variability in the time to reach steady state, which was predicted to be up to ∼3 weeks in some individuals (95% prediction interval: 18.6–297 h). Conclusions: The findings of this study have important implications for drug development. The lack of a clear dose-response relationship, due to large pharmacokinetic variability, indicates that a one-size-fits-all approach to CBD dosing may not be feasible, at least with current dosing approaches. Furthermore, an extended time to reach steady state means that the full effect of a selected dose level is not truly observed for some time and requires careful consideration in trial design.
dc.identifier.citationCannabis and Cannabinoid Research, 2023; 8(5):877-886
dc.identifier.doi10.1089/can.2021.0202
dc.identifier.issn2378-8763
dc.identifier.issn2378-8763
dc.identifier.urihttps://hdl.handle.net/11541.2/30015
dc.language.isoen
dc.publisherMary Ann Liebert
dc.relation.fundingBod Australia Pty Ltd.
dc.relation.fundingCancer Council's Beat Cancer Project on behalf of its donors, the State Government through the Department of Health
dc.relation.fundingAustralian Government through the Medical Research Future Fund
dc.rightsCopyright 2022 Mary Ann Liebert, Inc., publishers Access Condition Notes: Accepted manuscript available after 01 July 2023
dc.source.urihttp://doi.org/10.1089/can.2021.0202
dc.subjectcannabidiol
dc.subjectpharmacokinetics
dc.subjectmodeling
dc.subjectoral
dc.subjectabsorption
dc.subjectclinical
dc.titlePopulation pharmacokinetics of oral-based administration of cannabidiol in healthy adults: implications for drug development
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12249118020001831 13306149650001831 9916634125901831
ror.mmsid9916634125901831

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