Beechinor RJ, Thompson PA, Hwang MF, Vargo RC, Bomgaars LR, Gerhart JG, Dreyer ZE, Gonzalez D. The Population Pharmacokinetics of High-Dose Methotrexate in Infants with Acute Lymphoblastic Leukemia Highlight the Need for Bedside Individualized Dose Adjustment: A Report from the Children’s Oncology Group. Clin Pharmacokinet. 2019 Jul;58(7):899-910. doi: 10.1007/s40262-018-00734-0. PMID: 30810947; PMCID: PMC6658326.
Study ID Citation
Abstract
Infants with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate (MTX) may have reduced MTX clearance (CL) due to renal immaturity, which may predispose them to toxicity. The objective of this study was to develop a population pharmacokinetic (PK) model of MTX in infants with ALL. A total of 672 MTX plasma concentrations were obtained from 71 infants enrolled in the Children’s Oncology Group (COG) Clinical Trial P9407. Infants received MTX 4 g/m2 intravenously for four cycles during weeks 4–12 of intensification. A population PK analysis was performed using NONMEM® version 7.4. The final model was evaluated using a non-parametric bootstrap, a visual predictive check, and simulations were performed to evaluate MTX dosage and the utility of a bedside algorithm for dose individualization.