Pretreatment plasma folate modulates the pharmacodynamic effect of high-dose methotrexate in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma: "folate overrescue" concept revisited

. 2006 Apr ; 52 (4) : 692-700. [epub] 20060202

Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid16455868
Odkazy

PubMed 16455868
DOI 10.1373/clinchem.2005.061150
PII: clinchem.2005.061150
Knihovny.cz E-zdroje

BACKGROUND: To evaluate the influence of pretreatment plasma folate concentrations on methotrexate exposure in children with acute lymphoblastic leukemia/non-Hodgkin lymphoma treated with high-dose methotrexate, we assessed time profiles of plasma homocysteine, folate, and vitamin B(12) concentrations in children treated with high-dose methotrexate with leucovorin rescue. METHODS: We analyzed 98 treatment courses. The study endpoints were to determine how methotrexate exposure is related to homocysteine accumulation and whether it is influenced by pretreatment plasma folate. RESULTS: Peak concentrations of homocysteine increased from the start of the intravenous infusion through cessation of methotrexate therapy up to time point t(42), when this trend was reversed by administration of folinic acid. The area under the curve (AUC) for plasma homocysteine showed decreasing course-to-course tendencies with a statistically significant decrease only between courses 1 and 2 (P 10 nmol/L. Correspondingly, in the courses with low initial folate, peak plasma concentrations of methotrexate were significantly higher than in courses with high precourse concentrations of plasma folate. CONCLUSION: Endogenous pretreatment plasma folate modulates the magnitude of the methotrexate effect, providing support for a "folate overrescue" concept.

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