Pharmacokinetic Consideration of Biodrugs
INTRODUCTION Recent advancements in biotechnology enable us to create various kinds of recombinant bioactive proteins such as cytokines and antibodies as therapeutic drugs. Several drug-encapsulated carrier systems have also been created for efficient drug delivery. However, even if potent activity of synthetic proteins has been confirmed by in vitro experiments, their in vivo pharmacological effects are sometimes not sufficient for clinical use so that their clinical development is sometimes stopped. One of the critical reasons for the insufficiency is the inappropriate pharmacokinetic profile of biodrugs such as rapid elimination from blood circulation, small distribution to the pharmacological target, and unexpected distribution to a toxicological target that expresses the same receptors as the pharmacological target. The pharmacokinetics of regular low molecular weight drugs is mainly dominated by several kinds of metabolic enzymes and transporters, but the pharmacokinetic properties of biodrugs are distinct from those of regular drugs because their molecular weight is much higher. Thus, for the clinical development of biodrugs, it is important to know their pharmacokinetic properties in comparison with those of regular drugs. In this chapter, the mechanisms dominating the pharmacokinetics of biodrugs are described and the importance of mathematical modeling in understanding their pharmacokinetics is discussed.