Rectal bioavailability of Δ-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys

Article abstract of DOI:10.1002/jps.2600801008

Oral administration of Δ-9-tetrahydrocannabinal (Δ⁹-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. Δ⁹-THC-Hemisuccinate was formulated as a prodrug for Δ⁹-THC in suppositories using Witepsol H15 base. The bioavailability of Δ⁹-THC from this formulation was evaluated in monkeys. The plasma levels of Δ⁹-THC and its metabolite 11-nor-Δ⁹-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of Δ⁹-THC from this formulation was found to be 13.5%. Non-compartmental analysis of the plasma concentration data using statistical moments showed the mean residence time (MRT) for Δ⁹-THC in the body to be 3 h following iv administration of Δ⁹-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the Δ⁹-THC hemisuccinate. The observed rectal bioavailability of Δ⁹-THC from suppositories containing the hemisuccinate ester as a prodrug is of significant importance in developing an alternative approach to oral administration of the drug.