10.1002/jps.2600801008.abs 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.
Journal of Pharmaceutical Science – Wiley
Published: Oct 1, 1991
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