Saitoh H, Hatakeyama M, Eguchi O, Oda M, Takada M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
J Pharm Sci. 1998 Jan;87(1):73-5. doi: 10.1021/js970163u.
The interaction between steroid hormones and intestinal P-glycoprotein was investigated by measuring intestinal absorption from rat small intestine in situ. Prednisolone and hydrocortisone were rapidly absorbed from the entire small intestine. In contrast, methylprednisolone absorption was significantly retarded in jejunum and ileum by an intestinal efflux system. In the presence of verapamil an quinidine, the retarded absorption of methylprednisolone was completely recovered, suggesting that P-glycoprotein is responsible for the unique features of methylprednisolone absorption. A requisite for the substrate of intestinal P-glycoprotein seemed to be 6 alpha-methyl group in the steroid structure. Substrate specificity of intestinal P-glycoprotein to steroid hormones was shown to be in part different from those in other tissues such as adrenal gland. Little of all three steroid hormones disappeared in the supernatant of mucosal homogenate from rat small intestine, indicating that intestinal metabolism of these steroid hormones was relatively small.
通过测量大鼠小肠原位肠吸收来研究甾体激素与肠道P-糖蛋白之间的相互作用。泼尼松龙和氢化可的松能迅速从整个小肠吸收。相比之下，甲基泼尼松龙在空肠和回肠的吸收因肠外排系统而显著延迟。在维拉帕米和奎尼丁存在的情况下，甲基泼尼松龙延迟的吸收完全恢复，这表明P-糖蛋白是甲基泼尼松龙吸收独特特征的原因。肠道P-糖蛋白底物的一个必要条件似乎是甾体结构中的6α-甲基基团。肠道P-糖蛋白对甾体激素的底物特异性在部分上与肾上腺等其他组织不同。三种甾体激素在大鼠小肠黏膜匀浆的上清液中几乎没有消失，这表明这些甾体激素的肠道代谢相对较少。
