Relationship between structural alerts in NSAIDs and idiosyncratic hepatotoxicity: an analysis of spontaneous report data from the WHO database

Drug Safety : an International Journal of Medical Toxicology and Drug Experience
Naomi Jessurun, E P van Puijenbroek

Abstract

Idiosyncratic drug reactions such as hepatotoxicity and blood dyscrasias represent one of the major causes of drug withdrawal from the market. According to the reactive metabolite (RM) concept, this may be due to the metabolic activation of structural alerts (SAs), functionalities in the drug molecule that are susceptible to bioactivation resulting in RMs. The relationship, however, between metabolic activation of SAs in drugs with in vivo toxicity measured as disproportionate reporting of adverse drug reactions (ADRs) to the WHO VigiBase™ database has never been studied. The objective of this study was to investigate whether reported associations of hepatotoxicity between NSAIDs with SAs and NSAIDs with mitigated SAs are disproportionately present in the ADR reporting VigiBase™ database of the WHO collaborating center (the Uppsala Monitoring Centre). The extent of disproportionality of these associations is compared with associations of NSAIDs and hemorrhage, an ADR not associated with the forming of RMs. We calculated the reporting odds ratios for five NSAIDs [bromfenac (withdrawn), lumiracoxib (withdrawn), diclofenac, ibuprofen, and naproxen] associated with the MedDRA preferred terms: hepatic failure, hepatic function abnor...Continue Reading

References

Jan 1, 1988·Annual Review of Pharmacology and Toxicology·L R PohlJ G Kenna
Sep 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A T BanksJ G Harter
Oct 17, 1998·European Journal of Clinical Pharmacology·A Alvarez-RequejoL H Arias
May 18, 1999·JAMA : the Journal of the American Medical Association·M A FriedmanL J Thompson
Dec 24, 2003·Drug Discovery Today·Dominic P Williams, B Kevin Park
Apr 22, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James B MangoldChristiane Rordorf
Jul 9, 2004·Drug Metabolism Reviews·Basuki Gunawan, Neil Kaplowitz
Jun 25, 2005·Current Drug Metabolism·Amit S KalgutkarShawn P Harriman
Nov 14, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ying LiWei Tang
Apr 25, 2008·Expert Opinion on Drug Metabolism & Toxicology·Christian SkonbergMark P Grillo
Dec 19, 2009·Handbook of Experimental Pharmacology·A SrivastavaB K Park
Sep 11, 2010·Biopharmaceutics & Drug Disposition·Sophie L ReganB Kevin Park

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Citations

Dec 14, 2016·AACN Advanced Critical Care·Leslie A HamiltonRachel E Collins

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