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

被引：9

作者：

Yonezawa, Atushi ^{[1
,2
]}

Otani, Yuki ^{[1
]}

Kitano, Toshiyuki ^{[3
,4
]}

Mori, Mayuko ^{[1
,2
]}

Masui, Sho ^{[1
,2
]}

Isomoto, Yui ^{[1
]}

Tsuda, Masahiro ^{[1
,2
]}

Imai, Satoshi ^{[1
]}

Ikemi, Yasuaki ^{[1
]}

Denda, Masaya ^{[1
,2
]}

Sato, Yuki ^{[1
]}

Nakagawa, Shunsaku ^{[1
]}

Omura, Tomohiro ^{[1
]}

Nakagawa, Takayuki ^{[1
]}

Yano, Ikuko ^{[1
,2
,5
]}

Hayakari, Makoto ^{[1
]}

Takaori-Kondo, Akifumi ^{[3
]}

Matsubara, Kazuo ^{[1
]}

机构：

[1] Kyoto Univ Hosp, Dept Clin Pharmacol & Therapeut, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan

[2] Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan

[4] Kitano Hosp, Dept Hematol, Osaka, Japan

[5] Kobe Univ Hosp, Dept Pharm, Kobe, Hyogo, Japan

来源：

PHARMACEUTICAL RESEARCH | 2019年 / 36卷 / 06期

关键词：

carbohydrate chain; LC/TOF-MS; pharmacokinetics; rituximab; therapeutic monoclonal antibody; CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; MONOCLONAL-ANTIBODY; THERAPEUTIC ANTIBODIES; CHOP CHEMOTHERAPY; ELDERLY-PATIENTS; DLBCL PATIENTS; NANO-SURFACE; PHARMACOKINETICS; PHARMACODYNAMICS;

D O I：

10.1007/s11095-019-2624-5

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：11

共 41 条

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