メトトレキサートの排泄と有害事象に及ぼすプロトンポンプ阻害薬併用の影響

抄録

Co-administration of methotrexate (MTX) and proton pump inhibitors (PPIs) is reported to increase serum MTX concentrations in patients receiving high-dose MTX therapy. However, the range of MTX high dosage is wide. We attempted to clarify the effects of PPIs co-administration on the elimination of MTX at the fixed dose of 1 g/m² in a retrospective cohort study of 46 patients with hematological malignancies who underwent a total of 91 cycles of chemotherapy. Data on gender, age, concomitant drugs, and laboratory test results were analyzed. The median and first to third quartile of MTX concentrations with and without PPI co-administration at 24, 48, and 72 h postdosing were 17.42 (14.75 - 22.34) vs 19.96 (14.97 - 23.10) (P = 0.627), 0.25 (0.15 - 0.42) vs 0.34 (0.17 - 0.96) (P = 0.159), and 0.06 (0.04 - 0.10) vs 0.07 (0.04 - 0.23) (P = 0.357), respectively. No statistically significant differences were observed in the number of patients with delayed MTX elimination with each PPI. Nausea (all grades) was significantly less frequent in patients receiving PPIs (38％ with vs 68％ without, P < 0.05). Multivariate analysis results indicated that differences in creatinine clearance (24 h after MTX administration and baseline) (OR, 0.92; 95％CI, 0.88 - 0.97), gender (OR, 4.95; 95％CI, 1.55 - 15.81), and age (OR, 1.04; 95％CI, 1.00 - 1.08) were risk factors for delayed MTX elimination. These findings suggest that PPI co-administration does not affect MTX elimination at the dose of 1 g/m², but could relief nausea associated with chemotherapy.