Sin Yin Lim1, Satish Sharan2, Sukyung Woo2. 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.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.
Authors: Cecilia L Bergeria; Tory R Spindle; Edward J Cone; Dennis Sholler; Elia Goffi; John M Mitchell; Ruth E Winecker; George E Bigelow; Ronald Flegel; Ryan Vandrey Journal: J Anal Toxicol Date: 2022-07-14 Impact factor: 3.220
Authors: Aleksandra Zielińska; Amanda Cano; Tatiana Andreani; Carlos Martins-Gomes; Amélia M Silva; Marlena Szalata; Ryszard Słomski; Eliana B Souto Journal: Int J Mol Sci Date: 2022-05-31 Impact factor: 6.208