A single-dose comparative bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers.

Abstract

198 Background: The capsule formulation of dronabinol, a pharmaceutical tetrahydrocannabinol (THC), is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-associated nausea/vomiting in patients with inadequate response to conventional antiemetics. A new oral formulation (i.e., dronabinol solution) was evaluated in a bioequivalence study versus currently marketed dronabinol capsules. Methods: In an open-label, 2-treatment, 2-sequence, 4-period, single-dose crossover study, healthy volunteers were randomized to receive 1 of 2 treatment sequences (T-R-T-R or R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsules). Dosing occurred after an overnight fast, with a minimum 7-day washout period between treatment periods. A validated liquid chromatography-tandem mass spectrometry method was used to determine plasma concentrations of dronabinol and the primary metabolite 11-OH-Δ9-THC. Results: Fifty-one of 52 enrollees had pharmacokinetic data for analysis. Mean pharmacokinetics were (oral solution vs capsule): Cmax (2.0 vs 2.4 ng/mL), median Tmax (1.0 vs 1.5 h), AUC0-∞ (3.8 vs 4.1 h∙ng/mL), and t1/2 (5.6 vs 3.1 h). The 2 formulations were bioequivalent with respect to maximum plasma concentration (Cmax; reference-scaled criteria) and area under the plasma concentration-time curve (from time zero to last measurable concentration and from time zero to infinity [AUC0-∞]; average bioequivalence) of dronabinol. The data for the 11-OH-Δ9-THC metabolite provide further support for the bioequivalence of the 2 products. Post hoc analysis demonstrated that all volunteers (100%) had detectable plasma dronabinol concentrations at 15 min with the oral solution compared with < 25% of volunteers for the capsules. Intra-individual variability was lower with oral solution versus capsules (for AUC0-∞, 13.5% vs 36.8%, respectively). Conclusions: Dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsules 5 mg, and exhibited quicker onset of detectable levels and lower intra-individual variability in comparison with dronabinol capsules 5 mg. Clinical trial information: NCT01448772.