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Pharmacokinetics of subcutaneous methotrexate
F M Balis1, J Mirro, G H Reaman
1Pediatric Branch, National Cancer Institute, Bethesda, MD 20892.
Summary
Subcutaneous methotrexate offers a reliable alternative to oral dosing, ensuring complete absorption and overcoming variable bioavailability issues. This method is well-tolerated in both animal models and children with leukemia.
Area of Science:
- Pharmacology
- Oncology
- Drug Delivery Systems
Background:
- Oral methotrexate administration can lead to variable absorption and dose-dependent saturation.
- Parenteral administration is explored as an alternative to improve methotrexate bioavailability.
Purpose of the Study:
- To evaluate the pharmacokinetics and tolerability of subcutaneous methotrexate compared to oral and intravenous routes.
- To assess subcutaneous methotrexate as a viable alternative for patients with acute lymphoblastic leukemia.
Main Methods:
- Pharmacokinetic studies in Rhesus monkeys comparing subcutaneous, intravenous (IV), and oral methotrexate.
- Clinical monitoring of children with acute lymphoblastic leukemia receiving subcutaneous and oral methotrexate at different dosage levels.
Main Results:
- Subcutaneous methotrexate demonstrated complete absorption and a sustained-release effect compared to IV administration in monkeys.
- In children, subcutaneous methotrexate was fully absorbed, while oral administration showed significantly lower total drug exposure at higher doses.
- No local or systemic toxicities were observed with subcutaneous methotrexate in either animal or human studies.
Conclusions:
- Subcutaneous administration of methotrexate is well-tolerated and effectively absorbed.
- This route overcomes the absorption variability and saturation issues associated with oral methotrexate.
- Subcutaneous methotrexate represents a promising parenteral alternative for leukemia maintenance therapy.