Evaluation of absorbability of poorly water-soluble drugs: validity of the use of additives.
Evaluation of absorbability of poorly water-soluble drugs: validity of the use of additives.
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难溶性药物吸收性的评价：添加剂使用的有效性。
DOI：
10.1248/bpb.23.838
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发表时间：
2000
影响因子：
2
通讯作者：
M. Hayashi
中科院分区：
文献类型：
--
作者：
E. Watanabe;R. Sudo;M. Takahashi;M. Hayashi
采用室内法测定了吲哚美辛（IDM）、曲氨萜烯（TAT）等水溶性较差的药物经添加剂增溶后的离体大鼠肠组织的表观膜渗透系数（Papp）。考察了添加剂脱氧胆酸钠（DOC）、聚乙二醇600 （PEG 600）、二甲基亚砜（DMSO）、乙醇（EtOH）、丙二醇（PG）和大鼠胆汁。它们的浓度是根据体内实验和生理发现的结果在适当范围内确定的。根据膜通透性与体内生物利用度的对应关系，我们评估了体外实验的有效性。结果表明，5%的DMSO和10%的PEG 600对膜的完整性没有影响，是最适合进行室内实验的添加剂。IDM组的Papp大于TAT组，说明口服各自的PEG 600溶液后体内生物利用度的顺序与之一致。因此，我们的体外系统获得的Papp可用于评估体内生物利用度。
Apparent membrane permeation coefficients (Papp) of poorly water-soluble drugs such as indomethacin (IDM) and triamterene (TAT) were obtained by the chamber method using an isolated rat intestinal tissue after solubilization of the drugs by additives. For the additives, sodium deoxycholate (DOC), polyethylene glycol 600 (PEG 600), dimethylsulfoxide (DMSO), ethanol (EtOH), propylene glycol (PG), and rat bile were examined. Their concentrations were determined in ranges considered to be appropriate from the results of in vivo experiments and physiological findings. From the correspondence between this membrane permeability and in vivo bioavailability, we evaluated the validity of our in vitro experiment. On the basis of these evaluations, it was shown that 5% DMSO and 10% PEG 600, which did not affect the membrane integrity, were most appropriate additives for chamber experiments. Papp of IDM was greater than that of TAT, indicating that the order corresponded with that of in vivo bioavailability after oral administration of their PEG 600 solutions. Accordingly, it was concluded that Papp obtained by our in vitro system can be used to assess the in vivo bioavailability.