title: Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys.
abstract: 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 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 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.
authors.affiliation: Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University 38677.
authors.forename: M A
authors.initials: MA
authors.lastname: ElSohly
authors.forename: D F
authors.initials: DF
authors.lastname: Stanford
authors.forename: E C
authors.initials: EC
authors.lastname: Harland
authors.forename: A H
authors.initials: AH
authors.lastname: Hikal
authors.forename: L A
authors.initials: LA
authors.lastname: Walker
authors.forename: T L
authors.initials: TL
authors.lastname: Little
authors.forename: J N
authors.initials: JN
authors.lastname: Rider
authors.forename: A B
authors.initials: AB
authors.lastname: Jones
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D008252:Macaca fascicularis; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D013488:Suppositories
chemical_list: D011355:Prodrugs; D013488:Suppositories; C072823:delta9-tetrahydrocannabinol hemisuccinate; D013759:Dronabinol