Early transient accumulation of methotrexate in the cerebrospinal fluid of rabbits after treatment with methotrexate and roentgen rays.

Concomitant application of intrathecal methotrexate (MTX) and cranial irradiation has been described as being able to cause brain abnormalities in patients with leukemia. In the investigation presented, rabbits were treated once weekly for 6 weeks with intraventricular MTX and irradiation. Cerebrospinal fluid (CSF) sampled at various time points after each treatment contained for the samples obtained 4 hours after treatment increasing amounts of MTX. This indicated a retardation in MTX clearance from the CSF. Such a retardation might contribute to the generation of brain abnormalities, although no data have as yet been obtained to prove this suggestion.