Adverse drug reactions idiosyncratic hepatotoxicity

Serum chemistry markers play an important role in hepatotoxicity evaluation in human and animal safety studies. The classic markers of hepatotoxicity are alanine aminotransferase (ALT), aspartate aminotrasnferase (AST) and alkaline phosphatase (ALP) [124—127]. Drug-induced hepatotoxicity can be difficult to assess in some circumstances. Hepatotoxic responses can be intrinsic (predictable, dose-related) or idiosyncratic (unpredictable, non-dose-related). ALT, AST and ALP are generally not useful for predicting idiosyncratic responses. The administration of some drugs, such as isoniazid, can lead to a high incidence of ALT elevation, but are tolerated by most patients without severe hepatotoxicity. Adverse drug reactions can be masked... 

Troglitazone represents a model of an idiosyncratic drug reaction that led to withdrawal from the market and to attempts to understand the mechanisms of such adverse drug reactions. This review summarizes the proposed molecular mechanisms of troglitazone hepatotoxicity based on both in vivo and in vitro studies. However, so far, there is no direct evidence indicating the precise mechanism of the toxicity. Many factors have been proposed to contribute to this idiosyncratic toxicity. 

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