Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis.
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 greater than or equal to 5.8 x 10(-7)M (P = 0.008) and a dosage of greater than or equal to 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 x 10(-7)M.
Wallace
C A
CA
Department of Pediatrics, University of Washington, Seattle.
Bleyer
W A
WA
Sherry
D D
DD
Salmonson
K L
KL
Wedgwood
R J
RJ
D000284:Administration, Oral; D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D013997:Time Factors; D000637:Transaminases / Q000097:blood
D000637:Transaminases; D008727:Methotrexate