Abstract
The cerebrospinal fluid (CSF) pharmacokinetics of methotrexate (MTX) after high-dose intravenous infusion was investigated in 15 children with acute lymphoblastic leukemia (ALL).
The concentrations of MTX in CSF and serum were monitored simultaneously at 6-hr and 24-hr after the initiation of MTX infusion for 47 times of infusion.
The concentration of MTX in CSF was ranged from 0.5 μM to 4.1 μM with dosage between 1.4 and 5.6 g/m2.
The transportation of MTX from systemic circulation to CSF was evaluated with the MTX CSF/serum % concentration ratio.
The CSF/serum % concentration ratio during MTX infusion of patients with central nervous system (CNS) leukemia (1.45) was significantly higher (P<0.001) than that of patients without leukemic CNS involvement (0.63).
Previous skull irradiation before 1.5∼2.0 years, had no influence on the MTX CSF/serum % concentration ratio.
These data suggested leukemic infiltration in meninges accelerated the transport of MTX from circulation to CSF. The monitor of CSF/serum % concentration ratio during MTX infusion was considered to be essential not only for setting up the safety and appropriate schedule of high-dose MTX therapy, but also for predicting the CNS leukemia.
