RECTAL BIOAVAILABILITY OF DELTA-9-TETRAHYDROCANNABINOL FROM THE HEMISUCCINATE ESTER IN MONKEYS

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