Christian Skonberg, J. Olsen, Kim G Madsen
2008
Citations
4
Influential Citations
55
Citations
Quality indicators
Journal
Expert opinion on drug metabolism & toxicology
Abstract
BACKGROUND Carboxylic acids constitute a large and heterogeneous class of both endogenous and xenobiotic compounds. A number of carboxylic acid drugs have been associated with adverse reactions, linked to the metabolic activation of the carboxylic acid moiety of the compounds, i.e., formation of acyl-glucuronides and acyl-CoA thioesters. OBJECTIVE The objective is to give an overview of the current knowledge on metabolic activation of carboxylic acids and how such metabolites may play a role in adverse reactions and toxicity. METHODS Literature concerning the formation and disposition of acyl glucuronides and acyl-CoA thioesters was searched. Also included were papers on the chemical reactivity of acyl glutathione-thioesters, and literature concerning possible links between metabolic activation of carboxylic acids and reported cellular and clinical effects. RESULTS/CONCLUSION This review demonstrates that metabolites of carboxylic acid drugs must be considered chemically reactive, and that the current knowledge about metabolic activation of this compound class can be a good starting-point for further studies on the consequences of chemically reactive metabolites.