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肿瘤治疗用治疗性单克隆抗体的药代动力学/药效学(PK/PD)关系:有何新进展?

Pharmacokinetics/Pharmacodynamic (PK/PD) relationship of therapeutic monoclonal antibodies used in oncology: what's new?

机构信息

Gustave Roussy Cancer Campus, Department of Ambulatory Care, Villejuif, F-94805, France.

Gustave Roussy Cancer Campus, Department of Pharmacology, Villejuif, F-94805, France.

出版信息

Eur J Cancer. 2020 Mar;128:103-106. doi: 10.1016/j.ejca.2020.01.004. Epub 2020 Feb 20.

Abstract

Monoclonal antibodies in oncology, used as targeted molecular therapy, linked to cytotoxic compound or directed against immune checkpoints, feature complex PKs essentially determined by their physicochemical characteristics. The increasing number of studies shows the existence of Pharmacokinetics/Pharmacodynamic (PK/PD) relationships for many of them. Although more studies, especially conducted in early clinical phases, are needed, existing studies highlight the need to integrate PK data for monoclonal antibodies in all phases of their development and the therapeutic management of patients with cancer. The current challenge is to identify non-responders as soon as possible. The use of monoclonal antibody dosage to determine the patient's PK profile and, as a result, the disease activity profile could therefore be an early predictive marker to help physicians optimise the strategy to be pursued, including dose adjustment, prolongation of the dose interval or even discontinuation of treatment.

摘要

肿瘤学中的单克隆抗体作为靶向分子治疗药物,与细胞毒性化合物偶联或针对免疫检查点,其具有复杂的药代动力学特性,主要由其物理化学特性决定。越来越多的研究表明,其中许多药物存在药代动力学/药效动力学(PK/PD)关系。尽管需要更多的研究,特别是在早期临床阶段进行,但现有的研究强调需要在开发的所有阶段以及癌症患者的治疗管理中整合单克隆抗体的 PK 数据。目前的挑战是尽快识别无反应者。使用单克隆抗体剂量来确定患者的 PK 特征,进而确定疾病活动特征,因此可能成为早期预测标志物,有助于医生优化所采用的策略,包括调整剂量、延长剂量间隔甚至停止治疗。

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