Resumen de Propuesta de un modelo de monitorización de metotrexato en dosis altas en pacientes adultos con leucemia linfoblástica aguda y linfoma no Hodgkin

Josep M. Nicolas Arfelis, Rafael Ferriols Lisart, M. Bosquet Sanz, Manuel Alós Almiñana

• Objective: To define a pharmacokinetic model for the monitoring of methotrexate (MTX) in adult patients with acute lymphoblastic leukemia or non-Hodgkin's lymphoma, that allows for the estimation, based on the obtained concentration 24 hours after the administration, of the time of exposure to potentially toxic concentrations. Material and Methods: Retrospective analysis of the serum concentrations of methotrexate and the estimation of the population's pharmacokinetic parameters by means of the two-phase Bayesian iterative method, assuming a bicompartimental model with a first-order elimination system. Results: The estimated population's pharmacokinetic parameters were: central volume (L/Kg): 0.50 ± 0.25; clearance (L/h/Kg): 0.16 ± 0.08; k12 (h-1): 0.02 ± 0.02; k21 (h -1): 0.07 ± 0.03. The necessary time to achieve potentially safe concentrations, [MTX] < 0.05 × 10-6 M, was significantly correlated to the estimated time, based on the MTX concentration at 24 hours, by means of the following equation: T[MTX] < 0.05 × 10-6M (h) = 1.29 × TESTIMATED (h) (r2 = 0.90). Conclusion: The proposed model allows to predict the exposition time to potentially toxic MTX concentrations. This way, the number of serum samples of MTX can be reduced and the therapeutic scheme with folinate can be designed, even anticipating the patient's discharge for his control at home