Linked Life Data

12021625

Source:http://linkedlifedata.com/resource/pubmed/id/12021625

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-5-21
pubmed:abstractText
This study examined the role of thiopurine methyltransferase (TPMT) polymorphism in the metabolism and clinical effects of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease and childhood leukemia. The current hypothesis is that the cytotoxic effects of thiopurines are caused by the incorporation of thioguanine nucleotides into DNA. In this context, S-methylation catalyzed by TPMT can be regarded as a competing metabolic pathway. The authors assayed the TPMT activity in red blood cells from 122 patients treated with azathioprine or 6-mercaptopurine (83 adults with inflammatory bowel disease and 39 children with acute lymphoblastic leukemia) and in 290 untreated controls (219 adult blood donors and 71 children). The concentrations of thioguanine nucleotides and methylthioinosine monophosphate were also assayed in red blood cells from the patients. The TPMT activity and the concentrations of methylthioinosine monophosphate and thioguanine nucleotides were higher in children than in adults. All children but no adult patient received concomitant methotrexate. Interaction between methotrexate and 6-mercaptopurine has been described, and may explain the results. Low TPMT activity in adult patients with inflammatory bowel disease correlated to an increased incidence of adverse drug reactions. However, there was no correlation between TPMT activity and the red blood cell concentrations of methylthioinosine monophosphate or thioguanine nucleotides, or between the concentrations of these metabolites and the occurrence of adverse effects. The results show that the role of thiopurine metabolism for drug effects is complex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0163-4356
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-8
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:12021625-6-Mercaptopurine, pubmed-meshheading:12021625-Adult, pubmed-meshheading:12021625-Age Factors, pubmed-meshheading:12021625-Antimetabolites, Antineoplastic, pubmed-meshheading:12021625-Azathioprine, pubmed-meshheading:12021625-Child, pubmed-meshheading:12021625-Drug Therapy, Combination, pubmed-meshheading:12021625-Erythrocytes, pubmed-meshheading:12021625-Female, pubmed-meshheading:12021625-Humans, pubmed-meshheading:12021625-Immunosuppressive Agents, pubmed-meshheading:12021625-Inflammatory Bowel Diseases, pubmed-meshheading:12021625-Male, pubmed-meshheading:12021625-Methotrexate, pubmed-meshheading:12021625-Methyltransferases, pubmed-meshheading:12021625-Polymorphism, Genetic, pubmed-meshheading:12021625-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:12021625-Thioinosine, pubmed-meshheading:12021625-Thionucleotides
pubmed:year
2002
pubmed:articleTitle
Differences between children and adults in thiopurine methyltransferase activity and metabolite formation during thiopurine therapy: possible role of concomitant methotrexate.
pubmed:affiliation
Department of Clinical Pharmacology, University Hospital, SE-58185 Linköping, Sweden.
pubmed:publicationType
Journal Article, Clinical Trial, Controlled Clinical Trial, Research Support, Non-U.S. Gov't