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Drug induced liver toxicity is a frequent cause of the failure of drugs during clinical development,and in some cases such toxicities are identified only after a drug has been introduced into clinical use.In vitro assays that could identify the potential for hepatotoxicity early in drug discovery could be used to identify those compounds with a greater chance of avoiding this problem,and thus reduce the hardship it can cause.It is believed that many hepatotoxins are first metabolically bioactivated to reactive intermediary metabolites which can covalently bind to nucleophilic entities on macromolecules resulting in disruption of essential cellular processes.Assays in which measurement of covalent binding to microsomal protein in vitro,using radiolabeled compounds and a threshold value,have been proposed as a useful approach to select compounds for further =development that will have a lower potential to cause toxicity (Evans,et al.,2004).