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

Abstract Purpose High-dose methotrexate is an effective treatment for adult and pediatric patients with acute lymphoblastic leukemia, osteosarcoma, and lymphoma. However, its clearance is highly variable, and delayed clearance can lead to significant toxicity. This study aimed to identify a population pharmacokinetic model that accurately characterizes high-dose methotrexate clearance in an adult population. Methods We developed a new population pharmacokinetic model using a training dataset der