Using the Absorption Cocktail Approach to Assess Differential Absorption Kinetics of Cannabidiol Administered in Lipid-Based Vehicles in Rats

Dvora Izgelov, Aviva Regev, Abraham J. Domb, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Lipid-based drug delivery systems have been vastly investigated as a pharmaceutical method to enhance oral absorption of lipophilic drugs. However, these vehicles not only affect drug bioavailability but may also have an impact on gastric emptying, drug disposition, lymphatic absorption and be affected by lipid digestion mechanisms. The work presented here compared the pharmacokinetic (PK) behavior of the non-intoxicating cannabinoid cannabidiol (CBD) in sesame oil vs. a self-nano emulsifying drug delivery system (SNEDDS). This investigation was conducted with a unique tool termed the "absorption cocktail approach". In this concept, selected molecules: metoprolol, THC, and ibuprofen, were coadministered with CBD in the SNEDDS and sesame oil. This method was used to shed light on the complex absorption process of poorly soluble drugs in vivo, specifically assessing the absorption kinetics of CBD. It was found that the concentration vs. time curve following CBD-sesame oil oral administration showed extended input of the drug with a delayed Tmax compared to CBD-SNEDDS. Using the "cocktail"approach, a unique finding was observed when the less lipophilic compounds (metoprolol and ibuprofen) exited the stomach much earlier than the lipophilic cannabinoids in sesame oil, proving differential absorption kinetics. Findings of the absorption cocktail approach reflected the physiological process of the GI, e.g., gastric retention, stomach content separation, lipid digestion, drug precipitation and more, demonstrating its utility. Nonetheless, the search for more compounds as suitable probes is underway.

Original languageAmerican English
Pages (from-to)1979-1986
Number of pages8
JournalMolecular Pharmaceutics
Volume17
Issue number6
DOIs
StatePublished - 1 Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.

Keywords

  • absorption
  • bioavailability
  • cannabinoids
  • lipid-based delivery system
  • pharmacokinetics

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