Biomaterial Database

Accumulation of methotrexate in systemic tissues after intrathecal administration. 1997

W A Bleyer, and J A Nelson, and B A Kamen

University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

OBJECTIVE To determine systemic concentrations of methotrexate (MTX) after intrathecal administration in a patient with active leptomeningeal cancer. METHODS Tissues were obtained at autopsy, as requested by the patient, for MTX analysis after 5 doses of the drug were injected into his cerebrospinal fluid (CSF) 6 to 21 days before death. A radioligand assay was used to measure the concentration of MTX in multiple tissues. RESULTS Outside the neuraxis, MTX was found in highest concentration in the liver, kidney, lymph nodes, and spleen. Lung and bone also had substantial concentrations. Skeletal muscle had the lowest concentrations of measurable drug and the drug was not detected in the heart. In retrospect, the patient's second course of systemic chemotherapy resulted in greater systemic toxicities because intrathecal MTX was given in conjunction with this course of treatment. In addition, hypersensitivity to intrathecal morphine may have been caused by concomitant intrathecal MTX therapy. CONCLUSIONS Physicians administering intrathecal MTX must be aware of the paradoxically greater systemic exposure of the drug after intrathecal administration than after systemic administration, the need to expect greater systemic toxicities of intrathecal MTX, and the possibility that it may induce a hypersensitivity to concomitant intrathecal morphine.

UI	MeSH Term	Description	Entries
D007278	Injections, Spinal	Introduction of therapeutic agents into the spinal region using a needle and syringe.	Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297	Male		Males
D008577	Meningeal Neoplasms	Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.	Intracranial Meningeal Neoplasms,Spinal Meningeal Neoplasms,Benign Meningeal Neoplasms,Leptomeningeal Neoplasms,Malignant Meningeal Neoplasms,Meningeal Cancer,Meningeal Neoplasms, Benign,Meningeal Neoplasms, Intracranial,Meningeal Neoplasms, Malignant,Meningeal Tumors,Neoplasms, Leptomeningeal,Neoplasms, Meningeal,Benign Meningeal Neoplasm,Cancer, Meningeal,Cancers, Meningeal,Intracranial Meningeal Neoplasm,Leptomeningeal Neoplasm,Malignant Meningeal Neoplasm,Meningeal Cancers,Meningeal Neoplasm,Meningeal Neoplasm, Benign,Meningeal Neoplasm, Intracranial,Meningeal Neoplasm, Malignant,Meningeal Neoplasm, Spinal,Meningeal Neoplasms, Spinal,Meningeal Tumor,Neoplasm, Benign Meningeal,Neoplasm, Intracranial Meningeal,Neoplasm, Leptomeningeal,Neoplasm, Malignant Meningeal,Neoplasm, Meningeal,Neoplasm, Spinal Meningeal,Neoplasms, Benign Meningeal,Neoplasms, Intracranial Meningeal,Neoplasms, Malignant Meningeal,Neoplasms, Spinal Meningeal,Spinal Meningeal Neoplasm,Tumor, Meningeal,Tumors, Meningeal
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000230	Adenocarcinoma	A malignant epithelial tumor with a glandular organization.	Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D000964	Antimetabolites, Antineoplastic	Antimetabolites that are useful in cancer chemotherapy.	Antineoplastic Antimetabolites