Related Experiment Videos
Systemic methotrexate exposure is greater after intrathecal than after oral administration
Bruce C Bostrom1, Gary R Erdmann, Barton A Kamen
1Department of Pediatric Hematology Oncology, Children's Hospitals and Clinics, Minneapolis, Minnesota, USA. bostrom@childrenshc.org
Purpose:
To compare systemic exposure after intrathecal and oral methotrexate administration.
Patients And 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.
Conclusion:
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.