Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
15454631
DOI
10.1093/rheumatology/keh401
PII: keh401
Knihovny.cz E-zdroje
- MeSH
- adenosin krev MeSH
- antirevmatika aplikace a dávkování terapeutické užití MeSH
- dítě MeSH
- erytrocyty metabolismus MeSH
- juvenilní artritida krev farmakoterapie MeSH
- kyselina polyglutamová analogy a deriváty krev MeSH
- lidé MeSH
- methotrexát aplikace a dávkování analogy a deriváty krev terapeutické užití MeSH
- mladiství MeSH
- průřezové studie MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosin MeSH
- antirevmatika MeSH
- kyselina polyglutamová MeSH
- methotrexát MeSH
- methotrexate polyglutamate MeSH Prohlížeč
OBJECTIVE: In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. RESULTS: Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.
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