Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.

ABSTRACT:

Aims

No population pharmacokinetic studies of high-dose methotrexate (HDMTX) have been conducted in infants with brain tumours, which are a vulnerable population. The aim of this study was to evaluate HDMTX disposition in these children to provide a rational basis for MTX dosing.

Methods

Patients received 4 monthly courses of HDMTX (5 g/m² or 2.5 g/m² for infants aged ≤31 days) as a 24-h infusion. Serial samples were analysed for MTX by an enzyme immunoassay method. Pharmacokinetic parameters were estimated using nonlinear mixed effects population modelling. Demographics, concomitant medications and genetic polymorphisms were considered as pharmacokinetic covariates while MTX exposure and patient age were considered as covariates for Grade 3 and 4 toxic

SUBMITTER: Panetta JC 

PROVIDER: S-EPMC7015755 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature