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  • Title: Hepatotoxicity and hepatic metabolism of available drugs: current problems and possible solutions in preclinical stages.
    Author: Giri S, Nieber K, Bader A.
    Journal: Expert Opin Drug Metab Toxicol; 2010 Aug; 6(8):895-917. PubMed ID: 20367107.
    Abstract:
    UNLABELLED: IMPORTANCE OF THE FILED: According to a 2006 survey report of pharmaceutical companies, hepatotoxicity was ranked first in terms of adverse events and it remains the most common reason for restriction or withdrawal of a drug from the market by the FDA. Although there are many reasons underlying drug-induced hepatotoxicity, one of the most important is hepatotoxicity induced by drug metabolites. AREAS COVERED IN THIS REVIEW: This review highlights the unexpected evidence showing that > 64 allopathic drugs out of 900 can induce potentially life-threatening hepatotoxicity with diverse clinical features. In parallel, we demonstrate the use of a two-compartment organotypical model for monitoring drug biotransformation and the status of parent drugs or drug metabolites (reactive or stable metabolites). WHAT THE READER WILL GAIN: The reader will gain knowledge of the importance of the two-compartment model with special reference to drug metabolites and become aware of the hepatotoxicity of a list of allopathic drugs, many of which are presently used without prescription. TAKE HOME MESSAGE: A central challenge regarding drug-induced hepatotoxicity is to understand drug metabolite formation because, although many parent drugs are not toxic, their metabolites can be toxic to liver cells following biotransformation.
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