Rectal bioavailability of delta-9-tetrahydrocannabinol from various esters.
The bioavailability of delta-9-tetrahydrocannabinol (delta 9-THC) from suppository formulations containing several polar esters was studied. The esters tested were the hemisuccinate, N-formyl alaninate, N-methyl carbamate, and methoxy acetate. These esters were administered to monkeys in both lipophilic and hydrophilic suppository bases, namely, Witepsol H15 and polyethylene glycol, respectively. Each suppository contained a dose equivalent to 10 mg delta 9-THC. Blood samples were analyzed for both delta 9-THC and its carboxylic acid metabolite (ll-nor-delta 9-THC-9-COOH) using gas chromatography/mass spectrometry. The data showed that, with the exception of the hemisuccinate, no delta 9-THC or its metabolite was detected in the blood samples using the Witepsol H15. Using polyethylene glycol, low levels of delta 9-THC and its metabolite were detected in blood for all esters tested. The levels, however, were lower than those observed with delta 9-THC hemisuccinate using Witepsol H15. Subsequent studies in the conscious dog using the hemisuccinate in Witepsol H15 showed 67% bioavailability of delta 9-THC with a linear response in the dose range equivalent to 5-20 mg of delta 9-THC. No significant bioavailability differences were found when delta 9-THC hemisuccinate ester was administered in various lipophilic bases (Hydrokote 25, Kaomel, Suppocire AIML, and Witepsol H15).
Elsohly
M A
MA
Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University 38677.
Little
T L
TL
Hikal
A
A
Harland
E
E
Stanford
D F
DF
Walker
L
L
D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D013759:Dronabinol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005079:Excipients; D008401:Gas Chromatography-Mass Spectrometry; D008252:Macaca fascicularis; D008297:Male; D013488:Suppositories
D005079:Excipients; D013488:Suppositories; D013759:Dronabinol