ADME for Therapeutic Biologics: What Can We Leverage from Great Wealth of ADME Knowledge and Research for Small Molecules

Abstract

This chapter presents a brief historical perspective on how the roles of drug metabolism and pharmacokinetics (DMPK) and the key enablers for studying the absorption, distribution, metabolism, and excretion (ADME) processes of small molecule (SM) drugs and their underlying mechanisms have evolved over time in order to influence internal de‐risking strategy and decisions. It reviews external factors, such as changing regulatory environments and evolving large molecule (LM) discovery and development landscape. The chapter also provides an overview of a DMPK concept analogy between SMs and LMs, as well as case examples to demonstrate the applicability of SM DMPK knowledge and experiences to LM drug discovery and development. The commonly used bioanalytical methods for the determination of LMs in biological fluids are ligand‐binding assays that are immunological in nature. These assays usually have an associated degree of nonspecificity.

An Inexpensive, In-House-Made, Microdialysis Device for Measuring Drug–Protein Binding

“…For the development of new drugs, steps have been taken in the past several decades to create high-throughput methods for traditional ADME (absorption, distribution, metabolism, and excretion) testing . These ADME tools are significant in estimating and understanding the pharmacokinetics and overall therapeutic action of a drug compound in preparation for more costly in vivo studies. , An important ADME parameter is the concentration of free drug in solution, i.e., that which is not bound to macromolecules including serum proteins. It is the free concentration of compound that dictates its biological potency on the drug-target as well as the rate of drug clearance by metabolic and excretion processes. , …”