7-hydroxymethotrexate and Liver-Failure

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects.. Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia.. 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis.. Therapeutic methotrexate serum concentrations (30-100µmol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05).. 5 g/m2 methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity.

Topics: Adolescent; Antimetabolites, Antineoplastic; Blood Proteins; Child; Child, Preschool; Chromatography, High Pressure Liquid; Creatinine; Drug Administration Schedule; Female; Humans; Kidney; Liver; Liver Failure; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Renal Insufficiency; Stomatitis; Time Factors; Treatment Outcome