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Wide variability in rheumatoid arthritis drug suggests alternative dosing should be considered
Date:11/4/2008

Methotrexate (MTX) is commonly used to treat rheumatoid arthritis (RA) and is suggested as the "anchor" drug in treating the disease. Despite its widespread use, the understanding of its mechanism of action and pharmacokinetics is limited. Since joint damage occurs early in the course of RA and is largely irreversible, understanding the time it takes for stable levels of MTX to be reached could be useful in effectively controlling RA and preventing long-term damage. A new study examining levels of MTX metabolites in red blood cells was published in the November issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home).

MTX is normally taken orally and is rapidly taken up into a variety of cells, including red blood cells, where it remains long after being eliminated from blood serum. Once inside red blood cells, the drug can assume up to five different forms, which are known as MTXGlu1-5 (MTX polyglutamates) These can be measured inside red blood cells and are thought to be representative of concentrations within other cells, such as lymphocytes. Within the cell, MTX polyglutamates bind to and inhibit several important enzymes, playing a role in a number of anti-inflammatory actions and pathways. The dose of MTX varies and is unpredictable from patient to patient, but because it disappears rapidly from blood plasma, measurement in plasma can't be used to monitor concentrations of the drug. However, MTX polyglutamate concentrations can be measured in red blood cells. Patients with RA are normally started on low doses of MTX, with increasing amounts based on response to treatment, but valuable time may be lost with this method, resulting in unnecessary joint damage.

Led by Lisa Stamp and Murray Barclay of the University of Otago in Christchuch, New Zealand and supported by the Health Research Council of New Zealand, researchers examined
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Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell
Source:Eurekalert

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