Bioavailability of methotrexate: implications for clinical use.

Area of Science:

• Pharmacokinetics
• Oncology

Background:

• Methotrexate is a chemotherapy agent used for various cancers.
• Understanding its oral absorption and pharmacokinetic profile is crucial for optimizing treatment.

Purpose of the Study:

• To compare the bioavailability of oral methotrexate syrup versus intravenous administration.
• To investigate the relationship between methotrexate pharmacokinetics, treatment response, and toxicity in cancer patients.

Main Methods:

• Oral and intravenous methotrexate doses were administered to six patients to assess absorption.
• Thirty-three patients receiving methotrexate for various tumors were monitored for treatment response and toxicity.
• Methotrexate half-life (t1/2), serum, and urine levels were measured.

Main Results:

• Oral methotrexate absorption was variable, with lower area under the curve compared to intravenous dosing.
• A significantly longer methotrexate half-life was observed in partial responders (9.2 h) versus non-responders (3.8 h).
• Mild toxicities like mucositis and diarrhea occurred, but severe toxicity was not observed and could not be predicted by dose or bioavailability.

Conclusions:

• Oral methotrexate syrup exhibits variable absorption and lower bioavailability than IV administration.
• Methotrexate half-life is a potential predictor of treatment response in cancer patients.
• Monitoring serum and urine methotrexate levels is valuable for assessing drug absorption, bioavailability, and predicting treatment outcomes.