Variability in the disposition of intraventricular methotrexate: a proposal for rational dosing

Despite the clinical experience with Ommaya reservoir-facilitated intraventricular methotrexate (MTX) therapy, established age-related dosage guidelines do not exist. In an attempt to design such a schedule, 49 courses of intra-Ommaya MTX (median dose, 6 mg) administered to 12 patients were studied. Using a fluorescence polarized immunoassay (TDx; Abbott, Dallas, TX), the median peak intraventricular CSF MTX concentration (CSF [MTX]) was 423 mumol/L. Median CSF [MTX] at 24 hours was 4.6 mumol/L, and at 48 hours was 1.05 mumol/L. Median MTX half-life (t1/2) was 5.7 hours. A CSF [MTX] greater than 1 mumol/L was maintained for 24 hours in all but one course and for 48 hours in half of the courses. No correlations were found between MTX dose, patient age, [MTX], t1/2 or prior therapy. Considerable intra- and interpatient variability was seen in MTX disposition, emphasizing the need to monitor [MTX] with each course. A schedule for intraventricular MTX with an initial dose of 6 mg and supplemental doses of 6, 4, or 2 mg at 24 and 48 hours according to serial measurements of intraventricular [MTX] should be initiated to provide a minimum CSF [MTX] of 1 mumol/L for 72 hours.