Elsohly M A, Little T L, Hikal A, Harland E, Stanford D F, Walker L
Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University 38677.
Pharmacol Biochem Behav. 1991 Nov;40(3):497-502. doi: 10.1016/0091-3057(91)90353-4.
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).
对含有几种极性酯的栓剂制剂中δ-9-四氢大麻酚（δ9-THC）的生物利用度进行了研究。所测试的酯类为半琥珀酸酯、N-甲酰丙氨酸酯、N-甲基氨基甲酸酯和甲氧基乙酸酯。这些酯类分别以亲脂性和亲水性栓剂基质给药于猴子，即分别为Witepsol H15和聚乙二醇。每个栓剂含有相当于10mg δ9-THC的剂量。使用气相色谱/质谱法分析血样中的δ9-THC及其羧酸代谢物（11-去甲-δ9-THC-9-COOH）。数据显示，除半琥珀酸酯外，使用Witepsol H15时在血样中未检测到δ9-THC或其代谢物。使用聚乙二醇时，在所测试的所有酯类的血样中均检测到低水平的δ9-THC及其代谢物。然而，这些水平低于使用Witepsol H15的δ9-THC半琥珀酸酯所观察到的水平。随后在清醒犬中使用Witepsol H15中的半琥珀酸酯进行的研究显示，δ9-THC的生物利用度为67%，在相当于5-20mg δ9-THC的剂量范围内呈线性反应。当δ9-THC半琥珀酸酯在各种亲脂性基质（Hydrokote 25、Kaomel、Suppocire AIML和Witepsol H15）中给药时，未发现显著的生物利用度差异。
