[Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies]
Katalin Csordás1, Olivér Eipel, Márta Hegyi
1Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest Tűzoltó u. 7-9. 1094.
Unlabelled:
Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects.
Aim:
Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia.
Patients And 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).
Conclusion:
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.
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