Related Experiment Videos
Clinical pharmacology of intermediate-dose oral methotrexate
Abstract:
The clinical pharmacology of intermediate-dose oral methotrexate (MTX) was studied in nine patients receiving 18 courses of treatment. Serum and urine MTX concentrations were measured by means of a competitive protein binding assay after oral aqueous solution (3 courses), 50-mg tablets (13 courses) or IV drug (2 courses) had been administered in four doses of 100 mg/m2 at 6-h intervals or in four doses of 200 mg/m2 at 6-h intervals and followed by citrovorum factor rescue. Levels above 150 ng/ml (3.3 x 10(-7) M) were maintained throughout all treatment cycles, with rapid disappearance of drug after the last dose. A 100% increase in administered dose resulted in only a 42% increase in the concentration-time level. Methotrexate was absorbed well from both aqueous solutions and 50-mg tablets, but serum levels after 50-mg tablets were only 20% of those achieved after IV administration. We conclude that significant serum MTX concentrations can be achieved for prolonged periods of time after oral administration of intermediate doses, but that the proportion of drug absorbed is much less than is seen with lower doses.
Insights
Oral methotrexate (MTX) achieves significant serum concentrations for extended periods. However, absorption is less efficient at higher oral doses compared to lower ones.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Oncology
Background:
- Methotrexate (MTX) is a key chemotherapeutic agent.
- Understanding the clinical pharmacology of intermediate-dose oral MTX is crucial for optimizing treatment.
- Previous studies have focused on lower doses or different administration routes.
Purpose of the Study:
- To investigate the clinical pharmacology of intermediate-dose oral methotrexate.
- To assess serum and urine MTX concentrations following oral and IV administration.
- To evaluate the impact of dose escalation on MTX levels and absorption.
Main Methods:
- Nine patients received 18 treatment courses.
- MTX concentrations measured using competitive protein binding assay.
- Administered via oral aqueous solution, 50-mg tablets, or IV drug.
- Dosing regimens included 100 mg/m2 or 200 mg/m2 at 6-h intervals with citrovorum factor rescue.
Main Results:
- Sustained serum MTX levels above 150 ng/ml throughout treatment cycles.
- Rapid drug elimination after the final dose.
- A 100% dose increase yielded only a 42% increase in concentration-time levels.
- Oral MTX (aqueous and tablets) showed good absorption, but 50-mg tablets achieved only 20% of IV administration serum levels.
Conclusions:
- Intermediate-dose oral methotrexate can achieve prolonged significant serum concentrations.
- Drug absorption is less efficient at higher oral doses compared to lower doses.
- Oral administration of MTX at intermediate doses is viable but less effective than IV for achieving peak serum levels.