Okumura S, Fukuda Y, Takahashi K, Fujita T, Yamamoto A, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Pharm Res. 1996 Aug;13(8):1247-51. doi: 10.1023/a:1016080723968.
The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique.
Phenol red and fluorescein isothiocyanate-labeled dextrans (FDs) with different molecular weights were chosen as water-soluble model drugs. Absorption enhancers used in this study were N-lauryl-beta-D-maltopyranoside (LM), linoleic acid-HC060 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA).
The permeability of drugs gradually decreased with increasing their molecular weights, and the absorption of phenol red significantly increased by these absorption enhancers. Among these additives, LM, MM and Na-Cap appeared to be more effective for enhancing the permeability of drugs than the others. Furthermore, we plotted the logarithm of apparent permeability coefficient (Papp) of these drugs against the logarithm of their molecular weights. There exists a good correlation between these parameters. We measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the transport experiment to examine the membrane integrity. The average Rm value was about 700 omega.cm2, and this value was maintained for 3 hr.
This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.
采用体外尤斯灌流室技术，研究药物在非洲爪蟾肺膜的通透性以及各种吸收促进剂对其吸收的影响。
选用酚红和不同分子量的异硫氰酸荧光素标记葡聚糖（FDs）作为水溶性模型药物。本研究中使用的吸收促进剂有N-月桂酰-β-D-麦芽糖苷（LM）、亚油酸-HC060混合胶束（MM）、甘氨胆酸钠（Na-GC）、癸酸钠（Na-Cap）、水杨酸钠（Na-Sal）和乙二胺四乙酸二钠（EDTA）。
药物的通透性随分子量增加而逐渐降低，这些吸收促进剂显著增加了酚红的吸收。在这些添加剂中，LM、MM和Na-Cap在增强药物通透性方面似乎比其他添加剂更有效。此外，我们绘制了这些药物的表观渗透系数（Papp）对数与其分子量对数的关系图。这些参数之间存在良好的相关性。在转运实验过程中，我们测量了非洲爪蟾肺膜的跨膜电阻（Rm）以检测膜的完整性。平均Rm值约为700Ω·cm²，且该值在3小时内保持稳定。
该方法有助于评估药物在肺膜的转运特性。
