Physiologically Based Pharmacokinetic (PBPK) Modeling of Fexofenadine and Assessment of Transporter DDIs of Fexofenadine with P-gp inducers and inhibitors

Authors: Suvarchala A, Graves RH, Lukacova V
Conference: AAPS
Keywords: AAPS2023, ACAT model, DDI models, gastroplus, PBPK modeling
Software: GastroPlus®
Division: PBPK

Purpose

Fexofenadine (FEX), a H1-receptor antagonist used in the treatment of allergic rhinitis and chronic idiopathic urticaria, undergoes minimal metabolism and transporters play a major role in its absorption and disposition. FEX is frequently used as a probe substrate for P-gp, which plays a significant role in the apical efflux in the intestine, liver and kidneys. FEX is also a substrate for OATP2B1 uptake transporter, which is relatively highly expressed in the apical membrane of enterocytes, and a renal uptake transporter OAT3. The purpose of this project was to develop a PBPK model for FEX which accounts for all the relevant mechanisms impacting FEX pharmacokinetics (PK) after IV and PO administration in healthy Caucasian and Japanese subjects. This model was then validated by predicting the effect of P-gp inducers and inhibitors Rifampicin (RIF), Itraconazole (ITZ), and Verapamil (VPL) on FEX PK.

By Suvarchala Avvari, Rebecca Graves, Viera Lukacova

AAPS 2023 PharmSci 360,Orlando, FL, October 22-25, 2023