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タイトル: | Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin’s Lymphoma |
著者: | Yonezawa, Atushi Otani, Yuki Kitano, Toshiyuki Mori, Mayuko Masui, Sho Isomoto, Yui Tsuda, Masahiro https://orcid.org/0000-0001-9474-5107 (unconfirmed) Imai, Satoshi Ikemi, Yasuaki Denda, Masaya https://orcid.org/0000-0001-6820-2328 (unconfirmed) Sato, Yuki Nakagawa, Shunsaku Omura, Tomohiro Nakagawa, Takayuki Yano, Ikuko Hayakari, Makoto Takaori-Kondo, Akifumi Matsubara, Kazuo |
著者名の別形: | 米澤, 淳 北野, 俊行 津田, 真弘 中川, 俊作 大村, 友博 矢野, 育子 髙折, 晃史 松原, 和夫 |
キーワード: | carbohydrate chain LC/TOF-MS pharmacokinetics rituximab therapeutic monoclonal antibody |
発行日: | Jun-2019 |
出版者: | Springer Nature |
誌名: | Pharmaceutical research |
巻: | 36 |
論文番号: | 82 |
抄録: | Purpose: Therapeutic antibodies have heterogeneities in their structures, although its structural alteration in the body is unclear. Here, we analyzed the change of amino acid modifications and carbohydrate chains of rituximab after administration to patients. Methods: Twenty B cell non-Hodgkin’s lymphoma patients who were treated with rituximab for the first time or after more than one year’s abstinence were recruited. Structural analysis of rituximab was carried out at 1 h after administration and at the trough by using liquid chromatography/time-of-flight-mass spectrometry. Plasma rituximab concentration and pharmacodynamic markers were also determined. Results: Of recruited twenty, 3 patients exhibited rapid rituximab clearance. Nine types of carbohydrate chains were detected in rituximab isolated from the blood. The composition ratios in some glycoforms were significantly different between at 1 h after administration and at the trough, although consisted amino acids remained unchanged. The patients with high clearance showed extensive alterations of glycoform composition ratios. However, pharmacodynamics makers were not different. Conclusion: Inter-individual variations in plasma concentrations of rituximab were found in some B-NHL patients. We could analyze a change in glycoforms of rituximab in the patients, and this finding may affect the pharmacokinetics of rituximab. |
著作権等: | This is a post-peer-review, pre-copyedit version of an article published in Pharmaceutical Research. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11095-019-2624-5. The full-text file will be made open to the public on 15 April 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/241257 |
DOI(出版社版): | 10.1007/s11095-019-2624-5 |
PubMed ID: | 30989405 |
出現コレクション: | 学術雑誌掲載論文等 |
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