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

Oral administration of Delta -9-tetrahydrocannabinal ( Delta super(9)-THC) was shown to result in low and erratic bioavailability, while the drug showed no bioavailability from various suppository formulations. Delta super(9)-THC-Hemisuccinate was formulated as a prodrug for Delta super(9)-THC in suppositories using Witepsol H15 base. The bioavailability of Delta super(9)-THC from this formulation was evaluated in monkeys. The plasma levels of Delta super(9)-THC and its metabolite 11-nor- Delta super(9)-THC-9-COOH were determined using GC/MS analysis. The calculated bioavailability of Delta super(9)-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 Delta super(9)-THC in the body to be 3 h following iv administration of Delta super(9)-THC or its hemisuccinate ester (3.4 and 2.7 h, respectively), as compared with 5.8 h following rectal administration of the Delta super(9)-THC hemisuccinate. The observed rectal bioavailability of Delta super(9)-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.