Cerebrospinal Fluid Pharmacokinetics of Intravenous High Dose-Methotrexate

Abstract

Objective: To study the cerebrospinal fluid pharmacokinetics of intravenously administered high dose-methotrexate (HD-MTX) and provide a solid fundament for clinical practice. Methods: MTX at a high dose ranging from 1.0 to 3.0 g per course was intravenously administered to 30 patients with malignant tumors. Blood and CSF samples were consecutively collected up to 36 h after the initiation of infusion (6 h). MTX concentrations were measured by using a reversed phase high-performance liquid chromatography (RP-HPLC) assay. Results: CSF MTX concentrations were (1.65±1.52)×10^-6, (4.3±3.34)×10^-7, (1.46±1.10)×10^-7 and (3.19±4.38)×10^-8 mol/L, respectively, at 0, 6, 12 and 24 h post infusion, and became undetectable at 36 h post infusion. The concentration-time curve of CSF MTX closely resembled that of the plasma MTX and fitted with the following linear regression equation: Ŷ=0.057 97+0.010 82X (Ŷ: CSF MTX concentration, X: Plasma MTX concentration, r=0.8357). Conclusion: CSF MTX was metabolized in a linear two-compartment model. Additionally, pharmacokinetic analysis of MTX levels indicated a positive correlation between CSF MTX and plasma MTX levels.