Elevated Systemic Elimination of Cimetidine in Rats with Acute Biliary Obstruction: The Role of Renal Organic Cation Transporter OCT2

• KURATA Tomohiko

  Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine

• MURAKI Yuichi

  Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine Department of Pharmacy, Mie University Hospital

• MIZUTANI Hideki

  Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine College of Pharmacy, Kinjo Gakuin University

• IWAMOTO Takuya

  Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine Department of Pharmacy, Mie University Hospital

• OKUDA Masahiro

  Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine Department of Pharmacy, Mie University Hospital

抄録

  Renal tubular secretion of cationic drugs is dominated by two classes of organic cation transporters, OCT2/SLC22A2 and MATE1/SLC47A1, localized to the basolateral and brush-border membranes of the renal tubular epithelial cells, respectively. However, little is known about the expression and function of these transporters in acute cholestasis. Systemic clearance of cimetidine was significantly higher in rats with bile duct ligation (BDL) for 24 hours than in sham-operated rats, with no significant changes in the volume of distribution between the groups. In addition, net tubular secretory clearance of cimetidine was significantly higher in the BDL rats compared with the sham rats, with no significant changes in the glomerular filtration rate. Moreover, the renal tissue-to-plasma concentration ratio of cimetidine was elevated in BDL rats, although the renal tissue-to-urine clearance ratio of cimetidine was not different between the two groups. The expression level of basolateral organic cation transporter rOCT2 protein in the kidney cortex was markedly higher in BDL rats than that in the sham rats, but that of H⁺/organic cation antiporter rMATE1 protein in the brush-border membranes was not significantly different between the two groups. These results demonstrate that the renal tubular secretion of cimetidine was increased by acute cholestasis, and this increase was attributable to elevated expression levels of rOCT2 but not of rMATE1 in the rat.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 25 (4), 328-334, 2010

  日本薬物動態学会

キーワード

• bile duct ligation
• organic cation transporter 2
• multidrug and toxin extrusion 1
• tubular secretion
• cimetidine

詳細情報

• CRID: 1390282680157654656
• NII論文ID: 10027583140
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.dmpk-10-rg-004
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300392?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300392?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2011117947
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
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