Titlebook: Optimizing the "Drug-Like" Properties of Leads in Drug Discovery; Ronald T. Borchardt,Edward H. Kerns,James L. Steve Book 2006 Springer-Ve

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Metabolic Activation-Role in Toxicity and Idiosyncratic Reactions,ole of chemically reactive metabolites has been well recognized (.). Type B reactions, also referred to as idiosyncratic or hypersensitivity reactions, have been the subject of extensive reviews in recent years (., .). These are generally believed to be immune mediated, and are not predictable from

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,Case History — Use of ADME Studies for Optimization of Drug Candidates, Vd) in the body, and cleared from the body through metabolism and excretion. The area under the drug plasma concentration versus time curve (AUC) provides an indirect assessment of the exposure level and duration of action of the therapeutic agent at the site of action (e.g. synovial fluid, tumor,

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Computational Models Supporting Lead Optimization in Drug Discovery,, it can increase metabolic clearance, thus making difficult sustaining the pharmacologically relevant systemic exposure. In contrast, permeability, in many cases, increases with increasing lipophilicity, favoring absorption (.; .). The actual result will be determined by the relative contributions

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Book 2006nd clinical development divisions were created within many companies during the 1980s and 1990s, Because of their isolation, scientists in the discovery research divisions often were advancing drug candidates into preclinical development that had marginal drug-like properties. For the purpose of thi