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

J Pharm Sci. 1991 Oct;80(10):942-5. doi: 10.1002/jps.2600801008.

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.

MeSH terms

  • Administration, Rectal
  • Animals
  • Biological Availability
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacokinetics*
  • Gas Chromatography-Mass Spectrometry
  • Macaca fascicularis
  • Male
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics*
  • Radioimmunoassay
  • Suppositories

Substances

  • Prodrugs
  • Suppositories
  • delta9-tetrahydrocannabinol hemisuccinate
  • Dronabinol