RRC ID 41530
著者 Oka A, Oda M, Saitoh H, Nakayama A, Takada M, Aungst BJ.
タイトル Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells.
ジャーナル Biol Pharm Bull
Abstract We recently reported that P-glycoprotein (MDR1) is capable of interfering with the absorption of methylprednisolone in the rat small intestine. This study was undertaken to examine the interaction between methylprednisolone and MDR1 using Caco-2 cells. The permeation of various steroid hormones (hydrocortisone, prednisolone, progesterone, beta-estradiol, and testosterone) was compared. The basolateral-to-apical (secretory) permeation of methylprednisolone was more than 3-fold greater than the apical-to-basolateral (absorptive) permeation. When verapamil (0.1 mm), a potent modulator of MDR1, was added to both apical and basolateral sides of Caco-2 cells, the absorptive permeation of methylprednisolone was increased and its secretory permeation was decreased. As a result, the secretory-oriented manner of methylprednisolone permeation almost completely disappeared. Prednisolone and hydrocortisone exhibited weaker secretory-oriented movement than did methylprednisolone. The secretory-oriented permeation of prednisolone and hydrocortisone was also diminished by the addition of verapamil. There was no significant directionality in progesterone permeation and the permeation of beta-estradiol and testosterone tended to be absorptive. These results appear to suggest that methylprednisolone, prednisolone, and hydrocortisone interact with MDR1 as the substrates. In contrast, there was no evidence that MDR1 was capable of potently interfering with the absorption of the sex hormones tested in this study, supporting our previous findings in the rat. It was further found that apically-added verapamil demonstrated a modulating effect on MDR1 function even at 5 microM.
巻・号 25(3)
ページ 393-6
公開日 2002-3-1
DOI 10.1248/bpb.25.393
PMID 11913542
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology* Caco-2 Cells Cell Membrane Permeability Humans Methylprednisolone / metabolism* Methylprednisolone / pharmacokinetics Verapamil / pharmacology
IF 1.863
引用数 24
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)