Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications

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.