Physiologically-Based Pharmacokinetic Modelling of Rivoceranib Parent and Metabolite to Project DDI Risk and Support Regulatory Decision-Making

Conference: DDI
Software: GastroPlus®
Division: Simulations Plus


The PBPK model for rivoceranib, an anticancer drug acting as a tyrosine kinase inhibitor (TKI) that selectively targets vascular endothelial growth factor receptor-2, and its main pharmacologically active hydroxylated metabolite M1-1, was developed employing data from clinical studies (SAD, MAD, food effect) and validated against clinical DDI studies with itraconazole (CYP3A4 inhibitor) and rifampicin (CYP3A4 inducer). The objective of this work was to assess DDI risk for rivoceranib by utilizing PBPK modeling in lieu of clinical studies. The steps performed are depicted in the Scheme.

By Jasmina Novakovica, Grace Fraczkiewicza, Seong H Jangb, Jeff Heckmanb, Bill Stricklandb, Mingyan Zhouc, Nassim Djeblid

DDI Marbach Castle Workshop, Jun. 4th – 6th, 2023, Lake Constance, Germany