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.
Strother
D R
DR
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN.
Glynn-Barnhart
A
A
Kovnar
E
E
Gregory
R E
RE
Murphy
S B
SB
D000293:Adolescent; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004343:Drug Implants; D006801:Humans; D007276:Injections, Intraventricular; D008727:Methotrexate / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D004343:Drug Implants; D008727:Methotrexate