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Title: Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin’s Lymphoma
Authors: Yonezawa, Atushi
Otani, Yuki
Kitano, Toshiyuki
Mori, Mayuko
Masui, Sho
Isomoto, Yui
Tsuda, Masahiro
Imai, Satoshi
Ikemi, Yasuaki
Denda, Masaya
Sato, Yuki
Nakagawa, Shunsaku
Omura, Tomohiro
Nakagawa, Takayuki
Yano, Ikuko
Hayakari, Makoto
Takaori-Kondo, Akifumi
Matsubara, Kazuo
Author's alias: 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
Keywords: carbohydrate chain
LC/TOF-MS
pharmacokinetics
rituximab
therapeutic monoclonal antibody
Issue Date: Jun-2019
Publisher: Springer New York LLC
Journal title: Pharmaceutical Research
Volume: 36
Thesis number: 82
Abstract: 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.
Rights: 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'.
This is not the published version. Please cite only the published version. 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。
URI: http://hdl.handle.net/2433/241257
DOI(Published Version): 10.1007/s11095-019-2624-5
PubMed ID: 30989405
Appears in Collections:Journal Articles

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