Pharmacokinetics of Peptides and Proteins

Abstract

Protein-based therapeutics represent a rapidly growing class of new therapeutics for numerous indications. Low permeability and susceptibility to proteolytic degradation limit their oral bioavailability, and hence they are commonly administered by intravenous, subcutaneous or intramuscular routes. The distribution of protein therapeutics is usually limited to the extracellular space and takes place mainly by the processes of convective transport. Proteins are mainly eliminated by nonspecific catabolic degradation carried out by the ubiquitous presence of proteases and peptidases in the body, with intracellular uptake as a major prerequisite. Immunogenicity is a frequently encountered challenge of protein therapeutics that can affect their disposition, efficacy and toxicity. Combination therapy with protein therapeutics may potentially lead to drug–drug interactions, though such clinical events have rarely occurred. Rapid scientific advancements, unmet medical needs and high profit margins have been some of the motivating factors for the rapid emergence of next-generation protein therapeutics. An understanding of the absorption, distribution, metabolism and excretion processes of protein therapeutics is critical for their successful development. Keywords: pharmacokinetics; peptide therapeutics; immunogenicity; allometry; drug delivery; ADME ; drug–drug interaction