What question did this study set out to answer?

Development and validation of high-dose methotrexate population pharmacokinetic models to inform clinical decisions on dosing

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Randomized trial develops a pharmacokinetic model for high-dose methotrexate clearance in adults, suggesting better dosing accuracy and monitoring.

The study aims to develop a population pharmacokinetic model for high-dose methotrexate clearance in adults to guide dosing decisions.
Developed a new pharmacokinetic model using a training dataset from 208 adult patients at Vanderbilt University Medical Center.
Evaluated predictive performance against external models using an independent test dataset.
Incorporated body surface area, serum creatinine, and sex as covariates in the model.
The new model predicted high-dose methotrexate clearance most accurately at the 24-hour concentration measurement.
Performed similarly at the 72-hour mark compared to an external model at 48 hours.
Recommended sequential use of the model for initial predictions, followed by Bayesian forecasting for adjustments.

Blackman et al. (2026) studied this question.

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Randomized trial develops a pharmacokinetic model for high-dose methotrexate clearance in adults, suggesting better dosing accuracy and monitoring.