Secretory Transport of Methylprednisolone Possibly Mediated by P-Glycoprotein in Caco-2 Cells
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概要
- 論文の詳細を見る
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 methyl-prednisolone and MDR1 using Caco-2 cells. The permeation of various steroid hormones (hydrocortisone, prednisolone, progesterone, β-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 (0.1mM), 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 β-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 5μM.
- 社団法人日本薬学会の論文
- 2002-03-01
著者
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齊藤 浩司
北海道医療大学薬学部
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齋藤 浩司
北海道医療大学薬学部薬剤学講座
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齊藤 浩司
北海道医療大学薬学部:札幌腎と薬剤研究会
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齊藤 浩司
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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OKA Ayako
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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ODA Masako
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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SAITOH Hiroshi
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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NAKAYAMA Akira
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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TAKADA Masahiko
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokka
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J.Bruce AUNGST
DuPont Pharmaceuticals
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小田 雅子
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Nakayama Akira
Department Of Internal Medicine Fukui Cardiovascular Center
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Oka Ayako
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Tanaka M
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Nakayama A
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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Oda Masako
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Takada Masahiko
Department Of Morphological Brain Science Faculty Of Medicine Kyoto University
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Nakayama A
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaid
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Nakayama Akira
Department Of Adoministration And Social Sciences Fukushima University
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Saitoh Hiroshi
Department Of Pediatrics Nihon University School Of Medicine
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Saitoh Hiroshi
Department Of Material Science And Technology Faculty Of Engineering Niigata University
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