Physiologically Based Pharmacokinetic (PBPK) Modeling of Pyrotinib to Understand the Impact of Interplay Between CYP3A4 and P-GP on its DDIs with CYP3A4 Inhibitors/Inducers

Authors: Vora TB, Fraczkiewicz G, Zhao K, Li S, Shen K, Liu M, Djebli N, Sun S, Zhou M
Conference: ISSX
Keywords: CYP3A4, DDIs, gastroplus, in vivo, PBPK modeling
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Background

  • Pyrotinib is a novel and irreversible dual pan-ErbB and tyrosine kinase inhibitor developed for treating HER2-positive advanced solid tumors.
  • Pyrotinib, a BCS Class III compound, is primarily metabolized by CYP3A4, and in vitro results suggested that it might be a substrate for P-gp efflux transporter.

By Tarang Vora, Grace Fraczkiewicz, Kaijing Zhao, Shaorong Li, Kai Shen, Miao Liu, Nassim Djebli, Shuyu Sun and Mingyan Zhou

Presented at ISSX/MDO 2022, September 11-14, 2022, Seattle, WA