Bernards C M
University of Washington School of Medicine, Department of Anesthesiology, Seattle 98195.
J Pharm Sci. 1994 May;83(5):620-2. doi: 10.1002/jps.2600830504.
Previous studies have demonstrated that (hydroxypropyl)-beta-cyclodextrin behaves as a slow-release reservoir when used as a vehicle for intrathecal administration of opioids. The goal of the current investigation was to determine if (hydroxypropyl)-beta-cyclodextrin might serve as a slow-release vehicle for epidural opioid administration as well. An in vitro diffusion cell model was used to determine the flux of morphine, fentanyl, alfentanil, and sufentanil through the spinal meninges of Macaque nemestrina monkeys in the absence or presence of varying concentrations of (hydroxypropyl)-beta-cyclodextrin. No concentration of cyclodextrin slowed the flux of any of the opioids through the meninges, indicating that (hydroxypropyl)-beta-cyclodextrin will not behave as a slow-release reservoir for these opioids in the epidural space. This finding suggests that the rate-limiting step in opioid transfer was diffusion through the meninges not dissociation of the opioid cyclodextrin complex. However, (hydroxypropyl)-beta-cyclodextrin significantly increased the flux of sufentanil through the meninges. Since sufentanil's hydrophobicity has previously been shown to impede its meningeal flux, this finding suggests that cyclodextrin effectively decreases sufentanil's hydrophobicity by formation of inclusion complexes in the aqueous environments of the spinal meninges.
先前的研究表明，（羟丙基）-β-环糊精用作鞘内注射阿片类药物的载体时，可作为缓释储库。本研究的目的是确定（羟丙基）-β-环糊精是否也可作为硬膜外阿片类药物给药的缓释载体。使用体外扩散池模型来测定在不存在或存在不同浓度的（羟丙基）-β-环糊精的情况下，吗啡、芬太尼、阿芬太尼和舒芬太尼通过猕猴的脊髓膜的通量。没有任何浓度的环糊精能减缓任何一种阿片类药物通过脑膜的通量，这表明（羟丙基）-β-环糊精在硬膜外腔中不会作为这些阿片类药物的缓释储库。这一发现表明，阿片类药物转运的限速步骤是通过脑膜的扩散，而不是阿片类-环糊精复合物的解离。然而，（羟丙基）-β-环糊精显著增加了舒芬太尼通过脑膜的通量。由于先前已表明舒芬太尼的疏水性会阻碍其通过脑膜的通量，这一发现表明环糊精通过在脊髓膜的水性环境中形成包合物有效地降低了舒芬太尼的疏水性。
