Résumé
High-dose methotrexate (MTX-HD) is the treatment of choice for lymphoid hematological malignancies. The inter- and intra-individual variability of MTX pharmacokinetics makes dosage individualization difficult. The creation of population pharmacokinetic models is one approach to better describe these variabilities.The main objective of this work is to carry out an external evaluation of the population pharmacokinetic models of MTX-HD described in the literature in order to find the most suitable models for our patient population and to validate a population pharmacokinetic model at the local level.We conducted a retrospective, single-center study on a cohort of 92 adult patients with lymphoid hematological malignancies whose MTX dosing was performed between February 2020 and December 2022. A review of the literature led to the selection of 15 population pharmacokinetic models. All models were satisfactory with acceptable predictive performance. We also developed a local bicompartmental model. Our results show that creatinine clearance according to CKDEPI and albuminemia are covariables significantly related to MTX-HD clearance. The assessment of the predictive performance of our local model was excellent, with no significant biases and an accuracy and precision that surpassed the other models analyzed.The main aim is to be able to routinely use a high-performance model enabling dosage adjustment to take account of individual patient factors, and to offer personalized medicine.