A slow-release methotrexate formulation for intrathecal chemotherapy.
Optimal anticancer treatment with cell cycle phase-specific antimetabolites requires a sustained maintenance of cytotoxic drug levels. However, drugs that can be administered intrathecally have short half-lives in cerebrospinal fluid (CSF) and require repeated administrations by lumbar punctures, which are painful and inconvenient. Implantable pumps are expensive and require surgery. In a rat model, a lipid-based formulation of methotrexate (Depo/methotrexate) was tested for extended maintenance of therapeutic CSF concentration after a single injection. The half-life of methotrexate in CSF after an intracisternal injection of Depo/methotrexate was 5.4 days compared to 0.30 days for unencapsulated methotrexate. This 18-fold increase in methotrexate half-life may make Depo/methotrexate useful for intrathecal chemotherapy of neoplastic meningitis.
University of California San Diego, Cancer Center, La Jolla 92103-0812.
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Chatelut
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Kim
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Kim
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D003692:Delayed-Action Preparations; D007278:Injections, Spinal / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D003692:Delayed-Action Preparations; D008727:Methotrexate