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Model-Based Analysis of Cannabidiol Dose-Exposure Relationship and Bioavailability.

  • Lim, Sin Yin1
  • Sharan, Satish2
  • Woo, Sukyung2
  • 1 Department of Pharmacy, Clinical and Administrative Sciences, University of Oklahoma Health- Sciences Center College of Pharmacy, Oklahoma City, Oklahoma.
  • 2 Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center College of Pharmacy, Oklahoma City, Oklahoma.
Published Article
Publication Date
Feb 14, 2020
DOI: 10.1002/phar.2377
PMID: 32058609


There is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose-exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption. Single-dose (range: 5-6000 mg) CBD plasma concentration-time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose-exposure proportionality assessment was performed, and a population-based meta-analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed-effects modeling. A three-compartment model with a Weibull or zero-order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation. Oral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed-state OM (6.2%) were similar, whereas it was lower in fasted-state OM (0.9%). The Weibull absorption model best described OS, OC, and fed-state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed-state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted-state OM was best described by a zero-order absorption for the duration of 1.71 hours. The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization. © 2020 Pharmacotherapy Publications, Inc.

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