Middle-Out Physiologically Based Pharmacokinetic Modeling to Support Pediatric Dosing Recommendation for Alectinib.

ABSTRACT: Adult patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small-cell lung cancer (NSCLC) are treated with 600 mg alectinib twice daily (BID) as first-line treatment. ALK positive solid and central nervous system (CNS) tumors are described in the pediatric population, with limited clinical data due to the rarity of the disease and challenges to determine the right dosing. This study aims to inform pediatric dose recommendations for alectinib by performing a middle-out physiologically based pharmacokinetic (PBPK) modeling approach, accounting for differences in absorption and enzyme maturation. The developed adult PBPK model is leveraging insights from two previously developed PBPK models (focusing on absorption and drug-drug interactions) and is complemented with newly gen

SUBMITTER: van Donge T 

PROVIDER: S-EPMC12167915 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature