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

• Published in: Cancer chemotherapy and pharmacology 2003-03, Vol.51 (3), p.256-260
• Main Authors: KINOSHITA, Akitoshi, KUROSAWA, Yoshihiro, KONDOH, Kensuke, SUZUKI, Toshio, MANABE, Atsushi, INUKAI, Takeshi, SUGITA, Kanji, NAKAZAWA, Shinpei
• Format: Article
• Language: English
• Subjects: Adolescent; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacokinetics; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Child; Child, Preschool; Drug Interactions; Female; Fluid Therapy; Humans; Infusions, Intravenous; Liver - drug effects; Liver - pathology; Male; Medical sciences; Methotrexate - administration & dosage; Methotrexate - pharmacokinetics; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Sodium - pharmacology
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-002-0565-9

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.