Concentration and Glycoform of Rituximab in Plasma of Patients with B Cell Non-Hodgkin’s Lymphoma

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  • 米澤, 淳
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University
  • 北野, 俊行
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • 津田, 真弘
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University･Department of HematologyKitano Hospital, Osaka
  • 中川, 俊作
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University
  • 大村, 友博
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University
  • 矢野, 育子
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • 髙折, 晃史
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University
  • 松原, 和夫
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Ikemi, Yasuaki
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Denda, Masaya
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University
  • Sato, Yuki
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Nakagawa, Shunsaku
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Omura, Tomohiro
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Nakagawa, Takayuki
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Yano, Ikuko
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital･Graduate School of Pharmaceutical Sciences, Kyoto University･Department of Pharmacy, Kobe University Hospital
  • Hayakari, Makoto
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
  • Takaori-Kondo, Akifumi
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University
  • Matsubara, Kazuo
    Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital

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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.

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