Abstract
Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into shortlived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.
Keywords: hepatotoxicity, skin reaction, blood dyscrasias, reactive metabolites
Current Drug Metabolism
Title: Are Chemically Reactive Metabolites Responsible for Adverse Reactions to Drugs?
Volume: 3 Issue: 4
Author(s): D. P. Williams, N. R. Kitteringham, D. J. Naisbitt, M. Pirmohamed, D. A. Smith and B. K. Park
Affiliation:
Keywords: hepatotoxicity, skin reaction, blood dyscrasias, reactive metabolites
Abstract: Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into shortlived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.
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Cite this article as:
Williams P. D., Kitteringham R. N., Naisbitt J. D., Pirmohamed M., Smith A. D. and Park K. B., Are Chemically Reactive Metabolites Responsible for Adverse Reactions to Drugs?, Current Drug Metabolism 2002; 3 (4) . https://dx.doi.org/10.2174/1389200023337423
DOI https://dx.doi.org/10.2174/1389200023337423 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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