title: 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 micromol/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.
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. shoda-tky@umin.ac.jp
authors: Hirofumi
authors: H
authors: Shoda
authors: Shigeko
authors: S
authors: Inokuma
authors: Noriyuki
authors: N
authors: Yajima
authors: Yoshiaki
authors: Y
authors: Tanaka
authors: Taminori
authors: T
authors: Oobayashi
authors: Keigo
authors: K
authors: Setoguchi
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D003404:Creatinine; D008727:Methotrexate