Recombinant protein drug metabolism and pharmacokinetics

Recombinant proteins represent a critically important class of biopharmaceuticals and are indispensable for the prevention and treatment of various clinical diseases. However, their in vivo disposal is far more complex than those of small-molecule drugs. Unfortunately, pharmacokinetic (PK) studies of recombinant proteins still lag far behind those of small molecules, and most investigations are limited to the determination of overall PK parameters, with insufficient exploration at the cellular and subcellular levels or in-depth mechanistic insights. Inadequate understanding of the PK and metabolic characteristics of recombinant proteins frequently leads to limited or diminished efficacy and suboptimal safety profiles in clinical practice. Moreover, with the emergence of a growing number of novel recombinant proteins in recent years, such as monoclonal antibodies and fusion proteins, the PK research of recombinant proteins has become increasingly extensive while also facing mounting new challenges. Therefore, this article focuses on the PKs and metabolic characteristics of both classical and novel recombinant proteins, as well as the factors affecting their in vivo disposal, in order to enhance their therapeutic efficacy and safety through optimization of their PKs. To our knowledge, no comprehensive review has systematically summarized the PK properties and metabolic mechanisms of recombinant proteins, which highlights the necessity of this review. Furthermore, mechanistic insights into the PKs of recombinant proteins, particularly their metabolic mechanisms, remain scarce and outdated. We hope this review can draw more attention to this vital yet understudied area and promote further in-depth exploration. SIGNIFICANCE STATEMENT: Recombinant proteins, as indispensable clinical therapeutic agents, face limitations in achieving better efficacy and safety due to insufficient understanding of their PKs. This systematic review elucidates the PKs and metabolic mechanisms of recombinant proteins in the body, along with associated influencing factors. The information provided herein aims to deepen the understanding of the PK properties and disposal mechanisms of recombinant proteins, thus maximizing their potential clinical values in disease prevention and treatment.