Nakayama A, Eguchi O, Hatakeyama M, Saitoh H, Takada M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Japan.
Biol Pharm Bull. 1999 May;22(5):535-8. doi: 10.1248/bpb.22.535.
The intestinal absorption of ten steroid hormones was evaluated in the rat small intestine, especially focusing on the interaction with intestinal P-glycoprotein (P-gp). Hydrocortisone, prednisolone, 6alpha-methylprednisolone, and dexamethasone (adrenocortical steroid hormones) all disappeared in a regional-dependent manner (duodenum>jejunum>ileum). The decreased rate of disappearance in the lower small intestine seemed to be due to the involvement of absorption barriers like P-gp. In contrast, all sex hormones including progesterone exhibited very high absorbability in the entire small intestine (duodenum=jejunum=ileum), possibly demonstrating the absence of restricted absorption by intestinal P-gp. Progesterone enhanced the rate of disappearance of vinblastine but did not affect 6alpha-methylprednisolone. In the presence of vinblastine and verapamil, on the other hand, the rate of disappearance of 6alpha-methylprednisolone increased significantly. It was demonstrated that there was a plural P-gp family, which had different substrate specificities, in the rat intestine and that steroid hormones interacted with them as substrates or inhibitors in a very complex manner.
在大鼠小肠中评估了十种甾体激素的肠道吸收情况，尤其关注其与肠道P-糖蛋白（P-gp）的相互作用。氢化可的松、泼尼松龙、6α-甲基泼尼松龙和地塞米松（肾上腺皮质甾体激素）均以区域依赖性方式消失（十二指肠>空肠>回肠）。小肠下段消失速率的降低似乎是由于P-gp等吸收屏障的参与。相比之下，包括孕酮在内的所有性激素在整个小肠（十二指肠=空肠=回肠）中均表现出非常高的吸收性，这可能表明不存在肠道P-gp限制吸收的情况。孕酮提高了长春碱的消失速率，但不影响6α-甲基泼尼松龙。另一方面，在长春碱和维拉帕米存在的情况下，6α-甲基泼尼松龙的消失速率显著增加。结果表明，大鼠肠道中存在多个具有不同底物特异性的P-gp家族，甾体激素以非常复杂的方式作为底物或抑制剂与它们相互作用。
