Bensalem Amina, Ternant David
Université de Tours, EA 7501 GICC, Tours, France.
Department of Medical Pharmacology, CHRU de Tours, Tours, France.
Clin Pharmacokinet. 2020 Jul;59(7):857-874. doi: 10.1007/s40262-020-00874-2.
The pharmacokinetics of monoclonal antibodies is highly variable among patients. Several factors of variability, referred to as covariates in pharmacokinetic modeling, are known to influence this variability, such as body size, sex, antigen mass, serum albumin levels, or the presence of anti-drug antibodies. We propose a quantitative overview of the occurrence of assessment and detection of the main covariates associated with monoclonal antibody pharmacokinetics by comprehensively examining all population pharmacokinetic studies of monoclonal antibodies in humans. If some covariates are often assessed and detected (such as body size, antigen mass, or serum albumin levels), others are less frequently assessed but still may be relevant (e.g., anti-drug antibodies or endogenous immunoglobulin G levels). There is still a large heterogeneity in the relevance, availability, measurement, coding, detection, and interpretation of covariates. These issues deserve thorough investigation, which will help to design the optimal dosing strategy for every monoclonal antibody during its entire lifespan.
单克隆抗体的药代动力学在患者之间存在很大差异。已知有几个变异因素，在药代动力学建模中称为协变量，会影响这种变异性，例如体型、性别、抗原量、血清白蛋白水平或抗药抗体的存在。我们通过全面审查所有关于人类单克隆抗体的群体药代动力学研究，对与单克隆抗体药代动力学相关的主要协变量的评估和检测情况进行了定量概述。如果某些协变量经常被评估和检测（如体型、抗原量或血清白蛋白水平），那么其他协变量虽较少被评估，但可能仍然相关（例如抗药抗体或内源性免疫球蛋白G水平）。协变量在相关性、可获得性、测量、编码、检测和解释方面仍存在很大的异质性。这些问题值得深入研究，这将有助于在每种单克隆抗体的整个生命周期内设计出最佳给药策略。
