title: [Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies].
abstract: Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects.
  
  
  OBJECTIVE
  Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest Tűzoltó u. 7-9. 1094.
authors.forename: Katalin
authors.initials: K
authors.lastname: Csordás
authors.forename: Olivér
authors.initials: O
authors.lastname: Eipel
authors.forename: Márta
authors.initials: M
authors.lastname: Hegyi
authors.forename: Monika
authors.initials: M
authors.lastname: Csóka
authors.forename: Eva
authors.initials: E
authors.lastname: Pap
authors.forename: Gábor
authors.initials: G
authors.lastname: Kovács
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D017093:Liver Failure / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D051437:Renal Insufficiency / Q000139:chemically induced / Q000517:prevention & control; D013280:Stomatitis / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001798:Blood Proteins; D003404:Creatinine; C011864:7-hydroxymethotrexate; D008727:Methotrexate