Abstract: In recent years, biotechnologically-derived peptides and proteins have developed into mainstream therapeutic agents.Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development as well as in clinical practice.The understanding of the pharmacokinetics and pharmacodynamics, including the dose-concentration-effect relationship, is crucial to any drug-including peptides and proteins-as it lays the foundation for optimal dosing regimen design and rational clinical application.Compared to traditional small molecule-based therapeutics, pharmacokinetic and exposure/response evaluations for peptide and protein therapeutics are frequently complicated by their similarity to endogenous peptides and proteins as well as nutrients, by their intimate involvement in physiologic processes on the molecular level, by their macromolecule character and immunogenicity, and by analytical challenges to identify and quantify them in the presence of a myriad of similar molecules.Peptides and proteins, unlike conventional small molecule drugs, are generally not therapeutically active upon oral administration, and selection of the most appropriate route of administration requires comprehensive knowledge of their absorption characteristics beyond physicochemical properties, including chemical and metabolic stability at the absorption site, immunoreactivity, passage through biomembranes, and active uptake and exsorption processes.Various distribution properties dictate whether peptide and protein therapeutics can reach optimum target site exposure in order to exert the intended pharmacological response.Binding phenomena and receptor-mediated cellular uptake may further complicate this issue.Elimination processes-a critical determinant for the drug' s systemic exposure-may follow a combination of numerous pathways, including renal and hepatic metabolism routes as well as generalized proteolysis and receptor-mediated endocytosis. Pharmacokinetic/pharmacodynamic (PK/PD) correlations for peptide and protein-based drugs are frequently convoluted by their close interaction with endogenous substances and physiologic regulatory feedback mechanisms.
The manuscript highlights some of the major pharmacokinetic properties and processes relevant for the majority of biologics and will provide examples of well characterized pharmacodynamic relationships for peptide and protein therapeutics.Appreciation of the pharmacokinetic and pharmacodynamic differences between therapeutic biologics and traditional small molecule drugs will empower the drug development scientist as well as the healthcare provider to handle, evaluate and apply these compounds in an optimal fashion during the drug development process as well as in applied pharmacotherapy

Key words: Pharmacokinetics, pharmacodynamics, biologics, drug development, peptides, proteins