dc.contributor.author |
Csordas, Katalin |
|
dc.contributor.author |
Hegyi, Márta |
|
dc.contributor.author |
Eipel, Olivér |
|
dc.contributor.author |
Müller, Judit |
|
dc.contributor.author |
Erdélyi, Dániel |
|
dc.contributor.author |
Kovács, Gábor |
|
dc.date.accessioned |
2016-09-14T14:04:36Z |
|
dc.date.available |
2016-09-14T14:04:36Z |
|
dc.date.issued |
2013 |
|
dc.identifier |
84873080402 |
|
dc.identifier.citation |
pagination=189-197;
journalVolume=24;
journalIssueNumber=2;
journalTitle=ANTI-CANCER DRUGS; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/2380 |
|
dc.identifier.uri |
doi:10.1097/CAD.0b013e32835b8662 |
|
dc.description.abstract |
We carried out a detailed comparative study of the pharmacokinetics and toxicity of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) after high-dose intravenous methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Overall, 65 children were treated with 5 g/m2/24 h MTX and 88 children were treated with 2 g/m2/24 h MTX according to ALL-BFM 95 and ALL IC-BFM 2002 protocols (mean age: 6.4 years, range 1.0-17.9 years). A total of 583 HD-MTX courses were analyzed. Serum MTX and 7-OH-MTX levels were measured at 24, 36, and 48 h, and cerebrospinal fluid (CSF) MTX levels were determined 24 h after the initiation of the infusion. The area under the concentration-time curve was calculated. Hepatotoxicity, nephrotoxicity, and bone marrow toxicity were estimated by routine laboratory tests. We investigated pharmacokinetics and toxicity in distinct age groups (< 6 and > 14 years). 5 g/m2/24 h treatments resulted in higher serum and CSF MTX and 7-OH-MTX levels (P < 0.05). The CSF penetration rate of MTX was independent of the MTX dose [2.3% (95% confidence interval: 1.7-2.5%) vs. 2.8% (95% confidence interval: 2.4-3%)]. The CSF MTX concentration was correlated with the 24 h MTX serum level (r = 0.38, P < 0.0001). Repeated treatments did not alter MTX or 7-OH-MTX levels. 7-OH-MTX levels were correlated with nephrotoxicity (r = 0.36, P < 0.0001). Higher MTX levels and toxicity occurred more frequently in children aged older than 14 years (P < 0.05). Therapeutic serum and CSF MTX concentrations can be achieved more reliably with 5 g/m2/24 h treatments. To predict the development of toxicity, monitoring of the level of the 7-OH-MTX is useful. Monitoring of pharmacokinetics is essential to prevent the development of severe adverse events in adolescents. |
|
dc.relation.ispartof |
urn:issn:0959-4973 |
|
dc.title |
Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia |
|
dc.type |
Journal Article |
|
dc.date.updated |
2015-11-20T09:42:47Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2214921 |
|
dc.identifier.wos |
000312534100010 |
|
dc.identifier.pubmed |
23187460 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.institution |
Semmelweis Egyetem |
|