TOXI 30 |
| Idiosyncratic drug reactions significantly increase the uncertainty of drug development. If we had a better mechanistic understanding it might be easier to develop a method to screen drug candidates. There is a large body of evidence to suggest that most such reactions are caused by reactive metabolites of drugs and most are immune-mediated; however, there is little definitive data. Furthermore, there are many different types of idiosyncratic reactions and it is likely that the mechanisms can vary significantly. Mechanistic studies are very difficult but we have two models in which the adverse reaction in animals appears to be very similar to the idiosyncratic reaction that occurs in some people. These models are penicillamine-induced autoimmunity in the Brown Norway rat and nevirapine-induced skin rash in rats. In both models the reaction is immune-mediated and appears to involve covalent binding; however, there are also important mechanistic differences. |
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Drug Safety
2:00 PM-5:00 PM, Tuesday, August 21, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |