Pharmacokinetics of recombinant bifunctional fusion proteins.

INTRODUCTION: The development of biotechnology has enabled the creation of various recombinant fusion proteins as a new class of biotherapeutics. The uniqueness of fusion proteins lies in their ability to fuse two or more protein domains, providing vast opportunities to generate novel combinations of functions. Pharmacokinetic (PK) studies, which are critical components in preclinical and clinical drug development, have not been fully explored for fusion proteins. The lack of general PK models and study guidelines has become a bottleneck for translation of fusion proteins from basic research to the clinic. AREAS COVERED: This article reviews the current status of PK studies for fusion proteins, covering the processes that affect PK. According to their PK properties, a classification of fusion proteins is suggested along with examples from the clinic or under development. Current limitations and future perspectives for PK of fusion proteins are also discussed. EXPERT OPINION: A PK model for bifunctional fusion proteins is presented to highlight the importance of mechanistic studies for a thorough understanding of the PK properties of fusion proteins. The model suggests investigating the receptor binding and subsequent intracellular disposition of individual domains, which can have dramatic impact on the PK of fusion proteins.