Transport of Drugs Across the Xenopus Pulmonary Membrane and Their Absorption Enhancement by Various Absorption Enhancers
Transport of Drugs Across the Xenopus Pulmonary Membrane and Their Absorption Enhancement by Various Absorption Enhancers
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DOI：
10.1023/a:1016080723968
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发表时间：
1996-08
影响因子：
3.7
通讯作者：
S. Okumura;Y. Fukuda;Kanae Takahashi;T. Fujita;A. Yamamoto;S. Muranishi
中科院分区：
文献类型：
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作者：
S. Okumura;Y. Fukuda;Kanae Takahashi;T. Fujita;A. Yamamoto;S. Muranishi
目的。采用ANIN体外吸收小室技术考察药物对非洲爪哇肺膜的通透性及不同吸收促进剂对其吸收的影响。选用不同相对分子质量的酚红和荧光素异硫氰酸酯标记的右旋糖苷(FDs)作为水溶性模型药物。研究中使用的吸收促进剂有十二烷基吡喃-D-麦芽糖苷(LM)、亚油酸-HCO60混合胶束(MM)、糖胆酸钠(Na-GC)、戊酸钠(Na-β)、水杨酸钠(Na-SAL)和乙二胺四乙酸二钠(EDTA)。药物的渗透性随着其相对分子质量的增加而逐渐降低，这些吸收促进剂对苯酚红的吸收显著增加。在这些添加剂中，LM、MM和Na-Cap在提高药物通透性方面似乎比其他三种添加剂更有效。此外，我们还绘制了这些药物的表观渗透系数(Papp)的对数与其相对分子质量的对数。这些参数之间存在很好的相关性。在转运实验中，我们测量了非洲爪哇肺膜的跨膜阻力(Rm)，以检查膜的完整性。Rm值平均为70 0Ω·crn2，并可维持3h。该方法可用于估计药物在肺膜上的转运特性。
Purpose. The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using anin vitroUssing chamber technique.Methods. 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 wereN-lauryl-β-D-maltopyranoside (LM), linoleic acid-HCO60 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA).Results. 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 Ω·crn2, and this value was maintained for 3 hr.Conclusions. This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.