Population Pharmacokinetics of Ponatinib in Healthy Adult Volunteers and Patients With Hematologic Malignancies and Model-Informed Dose Selection for Pediatric Development.

ABSTRACT: The BCR-ABL1 inhibitor ponatinib is approved for the treatment of adults with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I mutation. We report a population pharmacokinetic model-based analysis for ponatinib and its application to inform dose selection for pediatric development. Plasma concentration-time data were collected from 260 participants (86 healthy volunteers; 174 patients with hematologic malignancies) enrolled across 7 clinical trials. Data were analyzed using nonlinear mixed-effects modeling. Ponatinib pharmacokinetics were described by a 2-compartment model with first-order elimination from the central compartment. The final model included body weight and age as covariates on the apparent central volum

SUBMITTER: Hanley MJ 

PROVIDER: S-EPMC9300170 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature