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

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 ± 0.8 h, and none of the patients showed a T_max of more than 4 h. 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 (0.16 µmol/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