Figure 3.

Influence of the dosage of methotrexate on arthritis scores in collagen‐induced arthritis rats when methotrexate was administered once a day. Methotrexate was orally administered at a dose of 0.1 (open diamonds), 0.25 (open squares), 0.5 (open triangles) and 1.0 (open circles) mg/kg once daily. Methotrexate was orally administered at a dose of 7.0 mg/kg once weekly (closed triangles) and 2.33 mg/kg thrice weekly (closed diamonds). Sodium bicarbonate was administered to the control group (closed squares). Each value represents the mean ± SD (n = 6–18). An arrow showed start date of methotrexate administration. **P < 0.01 and ***P < 0.001 vs the control group, ^# P < 0.05 and ^## P < 0.01 vs the once‐weekly group. Although the total dose per week in the 0.25 mg/kg once‐daily group was one‐quarter that in the thrice‐weekly group, arthritis scores in 0.25 mg/kg once‐daily group were markedly lower than in the thrice‐weekly group.