Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diffuse intrinsic pontine gliomas.

ABSTRACT:

Purpose

Crizotinib, a potent oral tyrosine kinase inhibitor, was evaluated in combination with dasatinib in a phase 1 trial (NCT01644773) in children with progressive or recurrent high-grade and diffuse intrinsic pontine gliomas (HGG and DIPG). This study aimed to characterize the pharmacokinetics of crizotinib in this population and identify significant covariates.

Methods

Patients (N = 36, age range 2.9-21.3 years) were treated orally once or twice-daily with 100-215 mg/m² crizotinib and 50-65 mg/m² dasatinib. Pharmacokinetic studies were performed for crizotinib alone after the first dose and at steady state, and for the drug combination at steady state. Crizotinib plasma concentrations were measured using a validated LC-MS/MS method. Population mode

SUBMITTER: Gibson EG 

PROVIDER: S-EPMC8561710 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature