Developmental pharmacokinetics of topotecan (TPT), a renally excreted drug, in infants and young children with brain tumors.

10055 Background: We investigated TPT pharmacokinetics (PK) in a clinical trial evaluating risk adapted therapy for infants and young children with brain tumors (NCT00602667). During consolidation, TPT is administered over 4 hrs to high risk patients on days 1 – 5; the initial dosage is based on age (patients 12 months receive 2, 2.5, and 3.5 mg/m2, respectively). Methods: PK studies are performed using a limited sampling strategy (time points: pre-infusion, 5 mins, 1, and 3 hours post infusion). TPT lactone concentrations are measured by HPLC-UV using a CLIA-approved assay. We use a PK-guided approach to individualize the TPT dosage to achieve a daily target plasma AUC0-∞ of 120 – 160 ng/mL*h. In this report we analyzed the individual TPT data from 38 patients using a population PK approach. A two-compartment PK model was fit to the TPT concentration-time data using nonlinear mixed effects modeling to estimate population PK parameters and inter- and intra-subject variability. Estimat...