Transition of average drug-to-antibody ratio of trastuzumab deruxtecan in systemic circulation in monkeys using a hybrid affinity capture liquid chromatography-tandem mass spectrometry

IF 1.7 4区医学 Q3 PHARMACOLOGY & PHARMACY

Biopharmaceutics & Drug Disposition Pub Date : 2023-08-03 DOI:10.1002/bdd.2371

Hiromi Habara, Hiromi Okamoto, Yoko Nagai, Masataka Oitate, Hideo Takakusa, Nobuaki Watanabe

引用次数: 0

Abstract

Trastuzumab deruxtecan (T-DXd, DS-8201a) is an antibody–drug conjugate, comprising an anti-HER2 antibody at a drug-to-antibody ratio of 7–8 with the topoisomerase I inhibitor DXd. In this study, the concentrations of antibody-conjugated DXd and total antibody were determined and observed to decrease over time following intravenous administration of T-DXd to monkeys. The drug-to-antibody ratio of T-DXd also decreased in a time-dependent manner, which reached approximately 2.5 in 21 days after administration. It was suggested that antibody-conjugated DXd of T-DXd was relatively stable in vivo compared with that of other reported antibody–drug conjugates.

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使用混合亲和捕获液相色谱-串联质谱法测定猴子体内循环中曲妥珠单抗-德鲁克斯替康的平均药物抗体比。

Trastuzumab deruxtecan（T-DXd，DS-8201a）是一种抗体-药物缀合物，包含与拓扑异构酶I抑制剂DXd的药物与抗体之比为7-8的抗HER2抗体。在本研究中，测定了抗体偶联的DXd和总抗体的浓度，并观察到在猴子静脉给药T-DXd后随着时间的推移而降低。T-DXd的药物与抗体的比率也以时间依赖的方式降低，在给药后21天达到约2.5。与其他报道的抗体-药物偶联物相比，T-DXd的抗体偶联DXd在体内相对稳定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biopharmaceutics & Drug Disposition 医学-药学

CiteScore

3.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Biopharmaceutics & Drug Dispositionpublishes original review articles, short communications, and reports in biopharmaceutics, drug disposition, pharmacokinetics and pharmacodynamics, especially those that have a direct relation to the drug discovery/development and the therapeutic use of drugs. These includes: - animal and human pharmacological studies that focus on therapeutic response. pharmacodynamics, and toxicity related to plasma and tissue concentrations of drugs and their metabolites, - in vitro and in vivo drug absorption, distribution, metabolism, transport, and excretion studies that facilitate investigations related to the use of drugs in man - studies on membrane transport and enzymes, including their regulation and the impact of pharmacogenomics on drug absorption and disposition, - simulation and modeling in drug discovery and development - theoretical treatises - includes themed issues and reviews and exclude manuscripts on - bioavailability studies reporting only on simple PK parameters such as Cmax, tmax and t1/2 without mechanistic interpretation - analytical methods