Characteristics of Pemetrexed Transport by Renal Basolateral Organic Anion Transporter hOAT3

• Material Type: 博士論文
• Title: Characteristics of Pemetrexed Transport by Renal Basolateral Organic Anion Transporter hOAT3
• Author/Editor: KURATA, Tomohiko
• Author Heading: KURATA, Tomohiko
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2016-03-25
• Publication Date (W3CDTF): 2016-03-25
• Alternative Title: 腎側低膜のヒト有機アニオントランスポーターｈOAT3によるペメトレキセドの輸送特性
• Degree grantor/type: 三重大学
• Date Granted: 2016-03-25
• Date Granted (W3CDTF): 2016-03-25
• Dissertation Number: 乙医学第993号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 乙医学第993号
• Text Language Code: eng
• Alias of Author: クラタ, トモヒコ; 倉田, 朋彦
• Subject Heading: pemetrexed; organic anion transporter; methotrexate; renal tubular secretion; drug interaction
• Target Audience: 一般
• Note (General): application/pdf; Purpose: Pemetrexed transport by human organic anion transporters, hOAT1 (SLC22A6) and hOAT3 (SLC22A8), were characterized in comparison with methotrexate. Methods: Accumulation of pemetrexed and methotrexate in hOAT1- and hOAT3-expressing cells were evaluated. Pemetrexed and methotrexate were determined by HPLC. Kinetic parameters were calculated by Eadie-Hofstee plot. Results: When HEK-hOAT3 and -hOAT1 cells were incubated with 100 μM pemetrexed for 30min, pemetrexed was accumulated at 14- and 1.7-fold greater than that in control cells, respectively. Pemetrexed and methotrexate transport by hOAT3 was saturated at high concentrations with apparent Km values 28.2 μM and 76.6 μM, respectively. In addition, intrinsic activity (Vmax/Km) of pemetrexed and methotrexate transport by hOAT3 was 4.82 and 0.42 μl/min/mg protein, respectively, suggesting 11-fold higher transport of pemetrexed than methotrexate by hOAT3. Furthermore, loxoprofen, ibuprofen, pravastatin, and cefazolin, transport substrates of hOAT3, inhibited pemetrexed transport by hOAT3 with IC50 values, 34.2, 27.9, 76.3 and 650 μM, respectively. Conclusions: Pemetrexed is a superior substrate to methotrexate for hOAT3. Loxoprofen, ibuprofen, and cefazolin could cause drug-drug interactions when attaining high blood concentrations.; 本文 / Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine; 6p; http://doi.org/10.2133/dmpk.DMPK-13-RG-042
• DOI: info:doi/10.2133/dmpk.DMPK-13-RG-042; https://doi.org/info:doi/10.2133/dmpk.DMPK-13-RG-042
• Persistent ID (NDL): info:ndljp/pid/10402952; https://dl.ndl.go.jp/pid/10402952
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-08-02T04:31:34+09:00
• Date Created (W3CDTF): 2017-07-04
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Related Material (URI): http://doi.org/10.2133/dmpk.DMPK-13-RG-042
• Periodical Title (URI): http://hdl.handle.net/10076/00016982; https://mie-u.repo.nii.ac.jp/records/11326
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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