Open AccessToxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis
Author(s) -
Wallace Carol A.,
Bleyer W. Archie,
Sherry David D.,
Salmonson Kathy L.,
Wedgwood Ralph J.
Publication year - 1989
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/anr.1780320604
Subject(s) - methotrexate , medicine , juvenile rheumatoid arthritis , dose , arthritis , toxicity , rheumatoid arthritis , gastroenterology , antifolate , transaminase , chemotherapy , antimetabolite , biochemistry , chemistry , enzyme
Abstract Twenty‐three children with destructive polyarticular juvenile rheumatoid arthritis (JRA) were treated for 0.5–4.3 years (median 1.6 years) with weekly doses of methotrexate (MTX) (0.11–0.6 mg/'kg/week). Serum levels of MTX at 1 hour and at 24 hours after drug administration were obtained at each dosage level and every 3 months after a stable dosage was achieved. No patient had serum levels of MTX that were in the toxic range nor evidence of hematologic, skin, mucous membrane, gastrointestinal, or pulmonary abnormalities. Ten patients had transiently elevated serum transaminase levels. Arthritis symptoms improved in 21 of these JRA patients, and the improvement was significantly associated with a mean 1‐hour serum MTX level of ≥5.8 × 10 −7 M ( P = 0.008)and a dosage of ≥0.3 mg/kg/week ( P = 0.004). The 1‐hour serum level of MTX was correlated with the MTX dosage (r = 0.28, P = 0.005). Our observations suggest that with close monitoring, MTX can be used safely at dosages as high as 0.6 mg/kg/week, and improvement in the symptoms of JRA will become evident when the serum levels of MTX 1 hour after administration approach 6.0 × 10 −7 M .