Variability in methotrexate serum and cerebrospinal fluid pharmacokineticsin children with acute lymphocytic leukemia: relation to assay methodologyand physiological variables

Methotrexate (MTX) steady state concentrations were evaluated in 42 childre n who had received high-dose infusions (6-8 g/m(2)) for acute lymphocytic l eukemia. Concentrations in serum and cerebrospinal fluid (CSF) measured by immunoassay were found to be highly variable. Reanalysis by a reference hig h-pressure liquid chromatography method ruled out analytical factors as a s ource of this variability. The correlation coefficient between the analytic al methods was 0.77 for the serum data and 0.88 for the CSF data. The varia bility of serum and CSF concentrations was higher in younger patients (seru m; P = 0.05 and CSF; P = 0.18), and the CSF concentration decreased with de creasing age and in later courses. Body surface area, body mass index, weig ht, and gender were not significantly related to MTX variability. We conclu de that the pronounced pharmacokinetic variability seen during MTX infusion s remains largely unexplained. (C) 2000 Elsevier Science Ltd. All rights re served.