Disease-related determinants of susceptibility to drug-induced idiosyncratic hepatotoxicity.
Idiosyncratic adverse drug reactions, including unpredictable hepatotoxicity, remain a serious challenge in drug development. Besides patient-specific susceptibility factors (genetic and/or acquired), determinants of the underlying disease may also predispose the patient to a drug's potential toxicity. Examples include viral infections, inflammatory conditions, neurodegenerative diseases and type II diabetes. This review focuses on diseases (therapeutic indications) often associated with mitochondrial abnormalities, and which are treated with drugs mechanistically linked to potential mitochondrial toxicity, thus superimposing these mitochondrial events. The need for an increased use of animal models of human disease in mechanistic investigations and drug candidate selection will also be emphasized.
Boelsterli
Urs A
UA
HepaTox Consulting, PO Box 14, CH-4148 Pfeffingen, Switzerland. boelsterli@hepatox.ch
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004194:Disease; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism