Intranasal absorption of Δ9-tetrahydrocannabinol and WIN55,212-2 mesylate in rats

The aim of this study was to examine the potential of the nasal route for systemic delivery of Δ9-tetrahydrocannabinol (Δ9-THC) and WIN55,212-2 mesylate. Anesthetized rats were surgically prepared to isolate the nasal cavity, into which Δ9-THC (10 mg/kg) or WIN55,212-2 (150 μg/kg) in propylene glycol alone or propylene glycol and ethanol (9:1) were administered. Rats were also administered Δ9-THC (1 mg/kg) and WIN55,212-2 (150 μg/kg) intravenously in order to determine absolute bioavailabilities of the nasal doses. Plasma Δ9-THC and WIN55,212-2 concentrations were determined by liquid chromatography/mass spectroscopy (LC/MS). The pharmacokinetics of the drugs after intranasal administration was best described by a one-compartment model with an absorption phase. WIN55,212-2 was absorbed more rapidly (Tmax = 0.2–0.3 h) than Δ9-THC (Tmax = 1.5–1.6 h) and to a higher extent than Δ9-THC. Addition of ethanol (10%) to the formulations had no significant effect on the Cmax after nasal administration (p > 0.05). Furthermore, it had no significant effect on the absolute bioavailability (Fabs): Fabs = 6.4 ± 2.4% and 9.1 ± 3.0% for Δ9-THC in propylene glycol, with and without ethanol, respectively. For WIN55,212-2, Fabs = 49.9 ± 6.9% (propylene glycol alone) and 56.6 ± 14.1% (propylene glycol with 10% ethanol). The results of the study showed that systemic delivery of Δ9-tetrahydrocannabinol and WIN55,212-2 could be achieved following nasal administration in rats.