Spinal cord penetration of intrathecally administered cytarabine and methotrexate: A quantitative autoradiographic study

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Abstract

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 sub-stantia 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. [J Natl Cancer Inst 1988;80:1211-1216].

Original languageEnglish (US)
Pages (from-to)1211-1216
Number of pages6
JournalJournal of the National Cancer Institute
Volume80
Issue number15
DOIs
StatePublished - Oct 5 1988

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Methotrexate
Cytarabine
Chemotherapy
Penetration
Spinal Cord
Drugs
Cancer
Drug Therapy
Rabbit
Complications
Meningeal Carcinomatosis
Pharmaceutical Preparations
Spinal Puncture
Spinal Cord Diseases
Poisons
Dependent
Neoplasms
Demonstrate
Rabbits
Therapeutics

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

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title = "Spinal cord penetration of intrathecally administered cytarabine and methotrexate: A quantitative autoradiographic study",
abstract = "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 sub-stantia 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. [J Natl Cancer Inst 1988;80:1211-1216].",
author = "Burch, {Patrick A.} and Grossman, {Stuart A} and Carla Reinhard",
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T1 - Spinal cord penetration of intrathecally administered cytarabine and methotrexate

T2 - A quantitative autoradiographic study

AU - Burch, Patrick A.

AU - Grossman, Stuart A

AU - Reinhard, Carla

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N2 - 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 sub-stantia 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. [J Natl Cancer Inst 1988;80:1211-1216].

AB - 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 sub-stantia 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. [J Natl Cancer Inst 1988;80:1211-1216].

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