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Rectal bioavailability of Δ‐9‐tetrahydrocannabinol from the hemisuccinate ester in monkeys

Rectal bioavailability of Δ‐9‐tetrahydrocannabinol from the hemisuccinate ester in monkeys 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Pharmaceutical Sciences Wiley

Rectal bioavailability of Δ‐9‐tetrahydrocannabinol from the hemisuccinate ester in monkeys

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Publisher
Wiley
Copyright
Copyright © 1991 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3549
eISSN
1520-6017
DOI
10.1002/jps.2600801008
Publisher site
See Article on Publisher Site

Abstract

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

Journal of Pharmaceutical SciencesWiley

Published: Oct 1, 1991

References