Drug Bioactivation and Oxidative Stress

摘要: Adverse drug reactions (ADRs) remain a major complication of therapy, account for significant number hospital admissions each year and contribute to patient morbidity mortality. These are issue the pharmaceutical industry, accounting attrition approximately one third compounds in development. Drug toxicity can mimic natural disease almost any body system be adversely affected by drugs. However, off-target or idiosyncratic represent problem industry because they add uncertainty process development ultimately lead withdrawal warnings labelling. They particularly difficult deal with likely discovered late after has been approved; this important implications as latter fails, more expensive is failure. Excessive dose, accumulation and/or formation chemically reactive metabolites (CRMs) have implicated many ADRs. Such usually rare not evident animal species, but serious even fatal humans may otherwise effective therapeutic agents. The fear such occurring at post-approval stage, when problems typically first become impediment At present, during preclinical evaluation there no accepted methods identification drugs that cause hypersensitivity humans. focus chapter will examine CRMs through normal phase I II metabolism, elucidate whether these species toxic, harmlessly detoxified excreted finally determine if chemical biological hallmarks hazard toxicity, used effectively screen out potentially dangerous earlier process. This use case-study examples which ADRs humans. Keywords: metabolism; bioactivation; chemically metabolite; adverse reaction; hepatotoxicity