chapter  8
22 Pages

Reactive Metabolites

Although it is essential for an organism to have enzymes that can convert lipophilic molecules into a form that can be eliminated as well as to convert toxic molecules to less toxic molecules, the process is not perfect and virtually any metabolic enzyme is also capable of converting some molecules to chemically reactive species that can be toxic. Chemically reactive metabolites can react with DNA, proteins, or other molecules leading to mutations, cancer, birth defects, and a variety of other types of toxicity. Therefore, it is important to understand the pathways that can lead to reactive metabolites and to be able to predict when a specific metabolite will be chemically reactive. In particular, many of the adverse reactions, especially idiosyncratic reactions caused by drugs, are believed to be due to reactive metabolites. For this reason, a major aspect of drug metabolism studies during drug development involves prediction of the potential that a drug candidate will form a reactive metabolite as well as screening drug candidates to determine if reactive metabolites are actually formed.