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Troglitazone Hepatotoxicity: Are We Getting Closer to Understanding Idiosyncratic Liver Injury?
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, MS 1018, 3901 Rainbow Boulevard, Kansas City, Kansas 66160
1 For correspondence via e-mail: hjaeschke@kumc.edu.
Received February 9, 2007; accepted February 12, 2007
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Idiosyncratic hepatotoxicity is a rare and unpredictable event of liver injury affecting generally less than 1 in 10,000 patients treated with certain drugs. However, it is a serious clinical problem as it accounts for 10% of all drug-induced liver failure cases (Kaplowitz, 2005
). Since idiosyncratic drug reactions are not detected in preclinical testing and in most cases not even during clinical trials, the problem surfaces generally after the drug is approved and hundreds of thousands of patients are being treated. Idiosyncratic hepatotoxicities are currently the main cause for Food and Drug Administration-mandated warnings, restrictions of use or even withdrawals of drugs from the market (Kaplowitz, 2005). As such, this is a considerable problem for the pharmaceutical industry and for regulatory agencies worldwide. One of the recent examples of drugs causing idiosyncratic hepatotoxicity and liver failure was the antidiabetic drug Rezulin (troglitazone).
Troglitazone, a peroxisome proliferator–activated