Physiologically Based Pharmacokinetic Model to Assess the Drug-Drug-Gene Interaction Potential of Belzutifan in Combination With Cyclin-Dependent Kinase 4/6 Inhibitors.

ABSTRACT:

Purpose

Belzutifan is a novel treatment for von Hippel-Lindau-associated cancers and is being evaluated in clinical trials for the treatment of renal cell carcinoma in combination with the cyclin-dependent kinase 4/6 inhibitors abemaciclib (ClinicalTrials.gov identifier: NCT04627064) and palbociclib (ClinicalTrials.gov identifier: NCT05468697). Belzutifan is metabolized via CYP2C19 and UGT2B17 and is a weak inducer of CYP3A. Induction of CYP3A is predicted to have a greater effect in dual CYP2C19/UGT2B17 poor metabolizers (PMs) relative to normal metabolizers (referred to as extensive metabolizers [EMs] in Simcyp). Our objective was to assess the drug-drug-gene interaction (DDGI) potential of belzutifan when coadministered with the CYP3A substrates abemaciclib and palbociclib in in

SUBMITTER: Meiman D 

PROVIDER: S-EPMC12917768 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature