Prediction of Human Pharmacokineticsfor Protein-Based Biologic Therapeutics

Scientists and researchers have put forth great effort over many decades into understanding the determinants of pharmacokinetics (PK) and trying to define a relationship between preclinical species and humans in order to perform reasonably accurate predictions. The similarities in drug ADME across mammalian species have been evaluated by numerous studies. Some fundamental approaches for prediction of human PK, namely interspecies scaling and physiologically-based PK (PBPK) modeling, have been proposed. Conventional interspecies allometric scaling is a classic, relatively simple mathematical approach that requires attaining relevant data from multiple animal species; selection of relevant preclinical species is critical. PBPK modeling fully incorporates anatomical, physiological, and biological factors relevant to ADME. PBPK models involve high computational complexity and require an extensive amount of high quality experimental data. The chapter also discusses these two commonly used approaches for prediction of human PK along with the accompanying concepts and rationale. Keywords: allometric scaling; human pharmacokinetics; interspecies scaling; PBPK modeling; protein-based biologic therapeutics