Effects of sodium in hydration solution on plasma methotrexate concentrations following high-dose methotrexate in children with acute lymphoblastic leukemia.

Purpose: To test whether a higher sodium dose in the hydration solution may facilitate faster methotrexate (MTX) elimination as compared with a lower sodium dose following high-dose MTX (HDMTX) treatment.

Methods: Intravenous solutions with alternate doses of sodium (regimen A 70 mEq/l, regimen B 100 mEq/l) were given to 30 children with acute lymphoblastic leukemia in two courses of HDMTX in a randomized crossover fashion. The plasma MTX concentrations every 24 h from the beginning of MTX administration and the adverse events associated with HDMTX were compared between the two hydration regimens.

Results: The plasma MTX concentrations were similar in the two hydration regimens at 24 h (A 50.9+/-7.4 vs B 40.9+/-5.4 microM, means+/- SE, P=0.17), but was significantly lower in regimen B at 48 and 72 h (A 0.65+/-0.17 vs B 0.27+/-0.03 microM, P=0.04; and A 0.14+/-0.03 vs B 0.05+/-0.01 microM, P=0.003). The time during which MTX plasma concentrations exceeded 0.1 microM was significantly longer in regimen A than in regimen B (A 3.83+/-0.18 vs B 3.13+/-0.06 days, P=0.001). The incidences of adverse events were similar between the two regimens ( P=0.78), and severe adverse events were not seen in either regimen.

Conclusions: Hydration with a higher sodium dose facilitated faster MTX elimination following HDMTX. Sodium may have a beneficial effect on MTX-induced nephrotoxicity.