Pharmacokinetic Monitoring of Methotrexate in Haematological Patients: Comparison of the Predictive Ability of Two Population-Based Models and Their Clinical Utility

Background and Objectives: Methotrexate (MTX) is a key drug for treating haematologic malignancies. Due to its narrow therapeutic window, Population pharmacokinetic (PopPK) models help predict MTX plasma concentrations (Cp) and optimize folinic acid rescue. This study evaluated and compared the predictive performance and clinical utility of two PopPK models in adults with lymphoma or acute lymphoblastic leukaemia (ALL).

Methods

A retrospective PK study was conducted in adults with lymphoma/ALL treated with MTX. Cp at 24 h (lymphoma) and 42 h (ALL) were estimated by Bayesian forecasting using the Gallais et al. (2021) and Kawakatsu et al. (2019) PopPK models with Levenberg–Marquardt least squares (M2) and Strict Adaptive Metropolis (SAA), using frequency-based (FB) or concentration-based (CB) weighting. Predictive performance was assessed using median percentage error (MDiPE), median absolute percentage error (MDiAPE), and the percentage of individual prediction errors within ±20% (iF20) and ±30% (iF30) of observed concentrations. Clinical utility was evaluated by concordance with folinic acid rescue.