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A slow-release methotrexate formulation for intrathecal chemotherapy
E Chatelut1, T Kim, S Kim
1University of California San Diego, Cancer Center, La Jolla 92103-0812.
Cancer Chemotherapy and Pharmacology
|January 1, 1993
Summary
A novel lipid-based methotrexate formulation significantly extends drug half-life in cerebrospinal fluid (CSF). This Depo/methotrexate may improve intrathecal chemotherapy for neoplastic meningitis, reducing painful lumbar punctures.
Area of Science:
- Oncology
- Pharmacology
- Neuroscience
Background:
- Effective anticancer treatment with antimetabolites necessitates sustained cytotoxic drug levels.
- Intrathecal chemotherapy drugs often have short half-lives in cerebrospinal fluid (CSF), requiring frequent, painful lumbar punctures or expensive implantable pumps.
Purpose of the Study:
- To evaluate a lipid-based methotrexate formulation (Depo/methotrexate) for extended CSF drug maintenance after a single intrathecal injection in a rat model.
- To assess the potential of Depo/methotrexate to improve intrathecal chemotherapy delivery and patient convenience.
Main Methods:
- Intracisternal injection of Depo/methotrexate and unencapsulated methotrexate in a rat model.
- Measurement of methotrexate half-life in CSF following administration.
Main Results:
- Depo/methotrexate demonstrated a significantly prolonged half-life of 5.4 days in rat CSF.
- Unencapsulated methotrexate had a significantly shorter half-life of 0.30 days in CSF.
- This represents an 18-fold increase in methotrexate half-life with the lipid-based formulation.
Conclusions:
- The lipid-based Depo/methotrexate formulation substantially increases methotrexate's half-life in CSF.
- Depo/methotrexate shows promise for simplifying intrathecal chemotherapy regimens for neoplastic meningitis.
- This formulation could reduce patient discomfort and healthcare costs associated with repeated lumbar punctures or pump surgeries.