title: Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers.
abstract: Dronabinol is a pharmaceutical tetrahydrocannabinol originally developed as an oral capsule. A dronabinol oral solution was recently approved, and the effects of food on absorption and bioavailability of the oral solution versus capsules were compared in an open-label, single-dose, 3-period crossover study. Healthy volunteers were randomized to either dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted). Dosing was separated by a 7-day washout period. Plasma pharmacokinetics were evaluated for dronabinol and its major metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-Δ9-THC). Pharmacokinetic data were available for analysis in 54 volunteers. In the fed state, initial dronabinol absorption was faster with oral solution versus capsule (mean time to the first measurable concentration, 0.15 vs 2.02 hours, respectively), with 100% and 15% of volunteers, respectively, having detectable plasma dronabinol levels 30 minutes postdose. There was less interindividual variability in plasma dronabinol concentration during early absorption with oral solution versus capsule. Compared with the fasted state, mean area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) increased by 2.1- and 2.4-fold for dronabinol oral solution and capsule, respectively, when taken with food. Mean time to maximum plasma concentration was similarly delayed for dronabinol oral solution with food (7.7 hours) and capsule with food (5.6 hours) versus capsule with fasting (1.7 hours). Under fed conditions, AUC0-tand area under the plasma concentration-time curve from time zero to infinity were similar for the oral solution versus capsule based on 11-OH-Δ9-THC levels. An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients, given its rapid and lower interindividual absorption variability versus dronabinol capsule.
authors.affiliation: INSYS Therapeutics, Inc., Chandler, AZ, USA.
authors.forename: D Alexander
authors.initials: DA
authors.lastname: Oh
authors.affiliation: INSYS Therapeutics, Inc., Chandler, AZ, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Parikh
authors.affiliation: INSYS Therapeutics, Inc., Chandler, AZ, USA.
authors.forename: Varun
authors.initials: V
authors.lastname: Khurana
authors.affiliation: INSYS Therapeutics, Inc., Chandler, AZ, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Cognata Smith
authors.affiliation: INSYS Therapeutics, Inc., Chandler, AZ, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Vetticaden
keywords: Marinol; bioavailability; dronabinol; observer variation; pharmacokinetics