Drug metabolism and pharmacokinetics in drug discovery: A primer for bioanalytica! chemists (Part I)

摘要

In the face of advancing technology in combinatorial synthesis and high throughput screening, the drug discovery process continues to evolve. Preclinical drug metabolism and pharmacokinetics studies play a key role in lead identification and optimization. Undesirable pharmacokinetic and metabolic features of drugs in human are a major reason for failure of a drug candidate. Investigating the metabolite formation, metabolic stability, and interaction with drug metabolizing enzymes has become crucial early on in the drug discovery process to weed out failures and continue the development of successes. The integration of drug metabolism studies into the drug discovery process requires testing drug candidates in human in vitro systems using microsomal fractions, hepatocytes and recombinant enzymes from human sources. Since this fast-paced development process has imposed an enormous burden on the analytical chemist to design faster and more-sensitive assay techniques to aid the in vitro drug metabolism studies in the pre-clinical stage, it is necessary for the analytical chemist to be familiar with fundamentals of the metabolism processes. In this article, the analytical chemist is introduced to the principles of drug metabolism.