ElSohly M A, Stanford D F, Harland E C, Hikal A H, Walker L A, Little T L, Rider J N, Jones A B
Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University 38677.
J Pharm Sci. 1991 Oct;80(10):942-5. doi: 10.1002/jps.2600801008.
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.
口服Δ⁹-四氢大麻酚（Δ⁹-THC）的生物利用度较低且不稳定，而该药物在各种栓剂剂型中均无生物利用度。Δ⁹-THC-半琥珀酸酯被配制成一种前药，用于以Witepsol H₁₅为基质的Δ⁹-THC栓剂。在猴子身上评估了该剂型中Δ⁹-THC的生物利用度。使用气相色谱/质谱分析测定了Δ⁹-THC及其代谢物11-去甲-Δ⁹-THC-9-COOH的血浆水平。发现该剂型中Δ⁹-THC的计算生物利用度为13.5%。使用统计矩对血浆浓度数据进行非房室分析表明，静脉注射Δ⁹-THC或其半琥珀酸酯后，体内Δ⁹-THC的平均驻留时间（MRT）分别为3小时（分别为3.4小时和2.7小时），而直肠给药Δ⁹-THC半琥珀酸酯后的平均驻留时间为5.8小时。观察到含有半琥珀酸酯作为前药的栓剂中Δ⁹-THC的直肠生物利用度对于开发该药物口服给药的替代方法具有重要意义。
