drugs and their metabolites

Abstract For many years the metabolism of drugs and other xenobiotics was equated with detoxification and inactivation. Since the early 1960s, it has been increasingly recognized that drugs and other xenobiotics can be metabolized to toxic and/or pharmacologically active as well as inactive metabolites. Traditionally, drug metabolites, that are compounds derived from the parent compound through Phase I and/or Phase II metabolic pathways, in general have not been routinely evaluated in cross-species safety assessments because their specific contribution to the overall toxicological potential of the parent drug has been unknown. The safety evaluation attempts be made to identify as early as possible during the drug development process differences in drug metabolism in animals used in nonclinical safety assessments compared to humans. The discovery of unique or major human metabolites late in drug development can cause development delays and could have possible implications for marketing approval. Early identification of unique or major metabolites will allow for timely assessment of potential safety issues. The FDA recommended four kinds of safety studies for assessing the safety of metabolites in Guidance for Industry Safety Testing of Drug Metabolites. The guidance can be performed to assess the safety of a unique or major metabolite. In this review, the main content of this guidance is introduced. Key words Drug metabolism; pharmacokinetics; metabolites; safety; evaluation testin