ABSTRACT
Active metabolite identification often occurs in various phases of the drug discovery and development process. This chapter examines some examples of active metabolites, each chosen because they reinforce one or more of the general conclusions that can be made regarding active metabolite formation. The addition of an alcohol to a drug at a position not critical for target binding may increase the metabolic stability and/or effect its intrinsic pharmacological activity. While epoxide metabolites are less likely to contribute to drug efficacy than hydroxylated ones, primarily due to their increased chemical reactivity and lower stability, there are some important examples of epoxides as active metabolites. Metabolite characterization is often hampered by either lack of a sufficient quantity of material for characterization and/or a robust separation procedure. Cost-effective approaches to identifying and characterizing active metabolites can be employed even during early stages of drug development.
