Different absorption behaviors among steroid hormones due to possible interaction with P-glycoprotein in the rat small intestine.
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.
Nakayama
A
A
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Kanazawa, Japan.
Eguchi
O
O
Hatakeyama
M
M
Saitoh
H
H
Takada
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006908:Hydroxyprogesterones / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008525:Medroxyprogesterone / Q000493:pharmacokinetics; D011374:Progesterone / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000493:pharmacokinetics*; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006908:Hydroxyprogesterones; D013256:Steroids; D011374:Progesterone; D014747:Vinblastine; D008525:Medroxyprogesterone