Systemic methotrexate exposure is greater after intrathecal than after oral administration.
OBJECTIVE
To compare systemic exposure after intrathecal and oral methotrexate administration.


METHODS
We analyzed red cell methotrexate polyglutamate concentrations with a sensitive radioligand-binding assay in 80 patients enrolled in the Children's Cancer Group (CCG) trial 1922 for acute lymphoblastic leukemia. Methotrexate concentrations were measured 7 days after the last doses of intrathecal and oral routes, using patients as their own controls. Intrathecal methotrexate was given on an age-adjusted schedule. Data was normalized to the actual dose received per body surface area.


RESULTS
The mean red cell methotrexate concentration 7 days after the last of four weekly intrathecal doses of methotrexate was 178 pmol/mL red blood cells, which was significantly greater than the result 7 days after subsequent weekly oral methotrexate of 122 pmol/mL (P = 0.00001). Intrathecal dosing resulted in an average systemic exposure ratio of 1.7 to 1 compared with oral administration.


CONCLUSIONS
Intrathecal methotrexate administration results in significantly greater systemic exposure than oral administration. Our data support the hypothesis that the systemic effect of intrathecal methotrexate affects ALL therapy.
Bostrom
Bruce C
BC
Department of Pediatric Hematology Oncology, Children's Hospitals and Clinics, Minneapolis, Minnesota, USA. bostrom@childrenshc.org
Erdmann
Gary R
GR
Kamen
Barton A
BA
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002675:Child, Preschool; D016001:Confidence Intervals; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate