Population Pharmacokinetics of High-Dose Methotrexate in Patients With Primary Central Nervous System Lymphoma

Abstract The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics are extremely large, and the pharmacokinetic property of MTX in patients with primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701 MTX plasma concentrations from 98 patients with PCNSL under high-dose MTX therapy were used to develop the population pharmacokinetic (popPK) model of MTX by using the nonlinear mixed-effects modeling method. A 2-compartment model was employed to describe the pharmacokinetic property of MTX. In the final popPK model, inclusion of serum creatinine and body surface area significantly reduced objective function value for clearance over the base model ( p V c ) over the base model ( p −0.48  × (BSA/1.75) 1.17 ; V c  = 24.46 × (age/57.16) 0.81 . The precision of all parameters was acceptable (relative standard error