Spinal cord penetration of intrathecally administered cytarabine and methotrexate: a quantitative autoradiographic study.
Carcinomatous meningitis is an increasingly common complication of systemic cancer. Treatment usually involves the use of intrathecal methotrexate or cytarabine, which have been reported to be toxic to the spinal cord. This study was performed to determine the penetration and distribution of intrathecally administered chemotherapy within the spinal cord. Tritiated methotrexate and cytarabine were administered intraventricularly and by lumbar puncture to New Zealand White rabbits. The extent and pattern of penetration of drug into the spinal cord were determined using quantitative autoradiographic techniques. The results demonstrate that 1 hour after administration 67%-99% of the total area of the spinal cord sections were exposed to these intrathecally administered agents. The pattern of distribution of the labeled drugs was inhomogeneous and was not dependent on the agent or the route of administration. High drug levels were seen in the area of the substantia gelatinosa and peripheral white matter which correspond to the location of pathological changes seen in the spinal cords of patients with neurotoxicity from intrathecal chemotherapy. This rapid and extensive penetration of intrathecally administered chemotherapy may offer insight into the myelopathy observed with these treatments.
Johns Hopkins Medical Institutions, Baltimore, MD.
P A
PA
Burch
S A
SA
Grossman
C S
CS
Reinhard
D000818:Animals; D001345:Autoradiography; D003561:Cytarabine / Q000493:pharmacokinetics* / Q000633:toxicity; D007278:Injections, Spinal; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000633:toxicity; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D003561:Cytarabine; D008727:Methotrexate