ORIGINAL ARTICLE

Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients

Authors

Hirofumi Shoda¹, Shigeko Inokuma², Noriyuki Yajima², Yoshiaki Tanaka², Taminori Oobayashi³ and Keigo Setoguchi²

1. Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2. Department of Allergy and Immunological Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
3. Department of Laboratory Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

Received:

07 November 2006

Accepted:

01 May 2007

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Abstract

Weekly pulsed low-dose methotrexate (MTX) is a standard regimen for rheumatoid arthritis (RA). Severe adverse reactions to MTX, such as pneumonia and cytopenia, sometimes occur; however, it is difficult to predict the development of these adverse reactions. In this article, we examine the serum concentrations of orally administered MTX of 69 Japanese patients with RA in the clinical setting. The maximum serum concentration (C max) after the first dose of the weekly administration and the time at which C max was obtained (T max) were analyzed. C max correlated with the administered dose before measurement. The average T max was 2.0 ± 0.8h, and none of the patients showed a T max of more than 4h. In addition, we demonstrated that the weekly MTX dosage and the mean dosage of steroids were significantly higher in patients with adverse reactions than in those without them, and the C max after the first dose of the weekly administration particularly correlated with the incidence of adverse reactions (P < 0.001). In fact, the cut-off point of C max (0.16μmol/l) was a sensitive predictor of the adverse reactions (sensitivity 81% and specificity 67%). We concluded that C max after the first dose of weekly administration is a useful parameter for predicting the development of adverse reactions to MTX.

Key words

Adverse reactions - Methotrexate - Pharmacokinetics - Rheumatoid arthritis