title: Metabolic activation of carboxylic acids.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Copenhagen, Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, Denmark. cs@farma.ku.dk
authors.forename: Christian
authors.initials: C
authors.lastname: Skonberg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Olsen
authors.forename: Kim Grimstrup
authors.initials: KG
authors.lastname: Madsen
authors.forename: Steen Honoré
authors.initials: SH
authors.lastname: Hansen
authors.forename: Mark P
authors.initials: MP
authors.lastname: Grillo
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002264:Carboxylic Acids / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D000214:Acyl Coenzyme A; D002264:Carboxylic Acids; D020719:Glucuronides; D004364:Pharmaceutical Preparations; D015262:Xenobiotics