Methotrexate inrheumatic diseases in children


Authors: P. Doležalová;  D. Němcová;  J. Chládek 1;  J. Krijt 2;  J. Hoza
Authors‘ workplace: Klinika dětského a dorostového lékařství 1. LF UK, Praha 1Oddělení farmakologie LF UK, Hradec Králové Ústav dědičných metabolických poruch 1. LF UK, Praha
Published in: Čes. Revmatol., , 2004, No. 3, p. 111-119.
Category:

Overview

Methotrexate (MTX) is one of the most effective and commonly used drugs in paediatric rheumato-logy. Both the total dose of MTX and its biological availability as well as the type and activity of metabolic processes involved determine the ultimate therapeutic efficacy. For the most rational and effective therapy knowledge of the principles of MTX pharmacokinetics is highly relevant mainly in terms of determination of individual dosing and route of administration. Children often need higher dose of MTX per surface area unit (10-15 mg/m2/week) than adults to achieve the clinical effect. In about 30-50 % of paediatric patients parenteral, usually subcutaneous administration is necessary. Due to the short biological half-life of free MTX it appears likely that long-lived MTX metabolites (polyglutamates), that reach their stable intracellular concentration within about 6 weeks of administration, are responsible for its long-term effects. The authors summarise results of erythrocyte MTX polyglutamate concentration measurments in patients treated with MTX for Juvenile Idiopathic Arthritis. Although it is likely that it reflects biological availability of MTX usefulness of MTX polyglutamate assessment in routine therapeutic monitoring needs to be further studied. Precise mechanism of MTX action is not fully understood. Results of experimental as well as clinical studies suggest its anti-inflammatory effect is mediated by different than anti-prolifera-tive mechanisms that are responsible mainly for its side effects. The authors present existing evidence for adenosine as the mediator of MTX anti-inflammatory action and show results of their own study dealing with blood adenosine assessment in the patients treated with MTX and matched paediatric controls. Effective MTX dose did not affect long-term adenosine concentration in treated patients. Possible explanations to this finding are discussed.

Key words:
Methotrexate, pharmacokinetics, mechanism of action, adenosine, juvenile idiopathic arthritis

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Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
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