Tipifarnib physiologically-based pharmacokinetic modeling to assess drug-drug interaction, organ impairment, and biopharmaceutics in healthy subjects and cancer patients.

ABSTRACT: A physiologically-based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and several clinical data in healthy subjects and cancer patients. The final PBPK model was able to recover the clinically observed single and multiple-dose plasma concentrations of tipifarnib in healthy subjects and cancer patients under several dosing conditions, such as co-administration with a strong CYP3A4 inhibitor and inducer, an acid-reducing agent (proton pump inhibitor and H2 receptor antagonist), and with a high-fat meal. In addition, the model was able to accurately predict the effect of mild or moderate hepatic impairment on tipifarnib exposure. The appropriately verified model was applied to prospectively simulate the

SUBMITTER: Okudaira N 

PROVIDER: S-EPMC11330181 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature