Weekly pulse therapy of methotrexate improves survival compared with its daily administration in MRL/lpr mice.
The purpose of this study was to determine whether weekly pulse therapy was superior to daily administration of methotrexate in MRL/lpr mice. Oral methotrexate was given to 6-week-old MRL/lpr mice at doses of 0.3, 1.0, or 3.0 mg/kg 5 days a week or at a dose of 15.0 mg/kg once a week until 35 weeks of age. The effects of methotrexate on physical, serological, and pathological findings were assessed. The survival rate and articular destruction on X-ray films were also evaluated. Both weekly pulse therapy and daily administration of methotrexate at the same weekly dose improved nephropathy and articular destruction of MRL/lpr mice when compared with control. However, weekly pulse therapy with methotrexate prolonged the survival of MRL/lpr mice when compared with the daily administration of the same weekly dose of methotrexate and control. Methotrexate did not suppress the increase in anti-DNA antibody and rheumatoid factor. Daily administration of methotrexate reduced the red and white blood cell counts, whereas weekly pulse therapy caused little reduction. In conclusion, weekly pulse therapy was superior to daily administration of methotrexate with respect to the survival rate, possibly due to a reduction in toxicity.
Asanuma
Yu
Y
Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kanagawa 216-8512, Kawasaki, Japan.
Nagai
Kasumi
K
Kato
Miyako
M
Sugiura
Hitoshi
H
Kawai
Shinichi
S
D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology; D007677:Kidney Function Tests; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D008206:Lymphatic Diseases / Q000209:etiology / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000209:etiology / Q000276:immunology; D011859:Radiography; D016019:Survival Analysis; D014508:Urea / Q000097:blood
D018501:Antirheumatic Agents; D001323:Autoantibodies; D014508:Urea; D008727:Methotrexate