The Metabolism of Anticancer Drugs by the Liver: Current Approaches to the Drug Development Process

The worldwide scientific community is in agreement that the activities of metabolic enzymes greatly impact the efficacies of anticancer drugs. Elucidation of the influences of these drugs on metabolism, especially that occurring in the liver, appears to be an extremely important step in the development of new anticancer drugs. Considering the continuous need to search for safe and effective chemotherapeutics, studies of the metabolism of new potent drugs are very important and should be included in the modern, innovative drug development pipeline. This article summarizes most of the current metabolic case studies involving anticancer drug development. Firstly, the impacts of diverse metabolic enzymes, particularly cytochrome P450, and the utilities of a few model in vitro enzymatic systems are described. Then, different analytical techniques, with particular emphasis on liquid chromatography- mass spectrometry detection and structural elucidation, are discussed. Finally, some computer-aided strategies for decisionmaking in the drug design process are described. Recent advances in drug development, including microdosing, in vitro-in vivo correlation and pharmacologic audit trail, are also discussed in relation to metabolic studies.