| pubmed-article:17303625 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0220806 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0034693 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0205103 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0025519 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0040377 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0205332 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:17303625 | lifeskim:mentions | umls-concept:C0597572 | lld:lifeskim |
| pubmed-article:17303625 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:17303625 | pubmed:dateCreated | 2007-4-20 | lld:pubmed |
| pubmed-article:17303625 | pubmed:abstractText | Carboxylic acids may be metabolized to acyl glucuronides and acyl-coenzyme A thioesters (acyl-CoAs), which are reactive metabolites capable of reacting with proteins in vivo. In this study, the metabolic activation of tolmetin (Tol) to reactive metabolites and the subsequent formation of Tol-protein adducts in the liver were studied in rats. Two hours after dose administration (100 mg/kg i.p.), tolmetin acyl-CoA (Tol-CoA) was identified by liquid chromatography-tandem mass spectrometry in liver homogenates. Similarly, the acyl-CoA-dependent metabolites tolmetin-taurine conjugate (Tol-Tau) and tolmetin-acyl carnitine ester (Tol-Car) were identified in rat livers. In a rat bile study (100 mg/kg i.p.), the S-acyl glutathione thioester conjugate was identified, providing further evidence of the formation of reactive metabolites such as Tol-CoA or Tol-acyl glucuronide (Tol-O-G), capable of acylating nucleophilic functional groups. Three rats were treated with clofibric acid (150 mg/kg/day i.p. for 7 days) before dose administration of Tol. This resulted in an increase in covalent binding to liver proteins from 0.9 nmol/g liver in control rats to 4.2 nmol/g liver in clofibric acid-treated rats. Similarly, levels of Tol-CoA increased from 0.6 nmol/g to 4.4 nmol/g liver after pretreatment with clofibric acid, whereas the formation of Tol-O-G and Tol-Tau was unaffected by clofibric acid treatment. However, Tol-Car levels increased from 0.08 to 0.64 nmol/g after clofibric acid treatment. Collectively, these results confirm that Tol-CoA is formed in vivo in the rat and that this metabolite can have important consequences in terms of covalent binding to liver proteins. | lld:pubmed |
| pubmed-article:17303625 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17303625 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17303625 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17303625 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17303625 | pubmed:month | May | lld:pubmed |
| pubmed-article:17303625 | pubmed:issn | 0090-9556 | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:HansenSteen... | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:BenetLeslie... | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:OlsenJørgenJ | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:BjørnsdottirI... | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:LiChunzeC | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:SideniusUlrik... | lld:pubmed |
| pubmed-article:17303625 | pubmed:author | pubmed-author:SkonbergChris... | lld:pubmed |
| pubmed-article:17303625 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17303625 | pubmed:volume | 35 | lld:pubmed |
| pubmed-article:17303625 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17303625 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17303625 | pubmed:pagination | 758-64 | lld:pubmed |
| pubmed-article:17303625 | pubmed:dateRevised | 2007-12-3 | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:meshHeading | pubmed-meshheading:17303625... | lld:pubmed |
| pubmed-article:17303625 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17303625 | pubmed:articleTitle | Studies on the metabolism of tolmetin to the chemically reactive acyl-coenzyme A thioester intermediate in rats. | lld:pubmed |
| pubmed-article:17303625 | pubmed:affiliation | Department of Pharmaceutics and Analytical Chemistry, the Danish University of Pharmaceutical Sciences, Copenhagen, Denmark. jqgo@novonordisk.com | lld:pubmed |
| pubmed-article:17303625 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17303625 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:17303625 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
