Kinoshita Akitoshi, Kurosawa Yoshihiro, Kondoh Kensuke, Suzuki Toshio, Manabe Atsushi, Inukai Takeshi, Sugita Kanji, Nakazawa Shinpei
Department of Pediatrics, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, 216-8511, Kawasaki, Japan.
Cancer Chemother Pharmacol. 2003 Mar;51(3):256-60. doi: 10.1007/s00280-002-0565-9. Epub 2003 Jan 17.
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.
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.
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.
Hydration with a higher sodium dose facilitated faster MTX elimination following HDMTX. Sodium may have a beneficial effect on MTX-induced nephrotoxicity.
测试与高剂量甲氨蝶呤（HDMTX）治疗后较低钠剂量相比，水化溶液中较高钠剂量是否可促进甲氨蝶呤（MTX）更快消除。
以随机交叉方式，在两个HDMTX疗程中，给30例急性淋巴细胞白血病儿童输注交替钠剂量的静脉溶液（方案A 70 mEq/l，方案B 100 mEq/l）。比较两种水化方案从MTX给药开始每24小时的血浆MTX浓度以及与HDMTX相关的不良事件。
两种水化方案在24小时时的血浆MTX浓度相似（A 50.9±7.4对B 40.9±5.4微摩尔，均值±标准误，P = 0.17），但在48小时和72小时时方案B中的浓度显著更低（A 0.65±0.17对B 0.27±0.03微摩尔。P = 0.04；以及A 0.14±0.03对B 0.05±0.01微摩尔，P = 0.003）。MTX血浆浓度超过0.1微摩尔的时间在方案A中比方案B显著更长（A 3.83±0.18对B 3.13±0.06天，P = 0.001）。两种方案之间不良事件的发生率相似（P = 0.78），且两种方案均未出现严重不良事件。
较高钠剂量的水化促进了HDMTX后MTX的更快消除。钠可能对MTX诱导的肾毒性有有益作用。
