Delineating the Role of Transporters in the Absorption and Disposition of Digoxin Using the Physiologically Based Pharmacokinetic (PBPK) Modeling

Authors: Avvari S, Chapa R, Adiwidjaja J, Graves RH, Lukacova V
Conference: AAPS
Keywords: AAPS2024, ACAT, biopharmaceutics classification system, drug-drug interactions (DDI)
Software: GastroPlus®

Purpose

Digoxin (DIG) is one of the cardiac glycosides that inhibits sodium-potassium ATPase, an enzyme that regulates the intracellular concentration of sodium and potassium. DIG falls under Class IV of the Biopharmaceutics Classification System (BCS), i.e., a low solubility and low permeability and is the most commonly recommended probe substrate to investigate the drug-drug interaction (DDI) potential of investigational drugs that are P-gp inhibitors and/or inducers. The absorption and disposition of DIG is governed by multiple transporters: P-gp, MDR3, OATP4C1, and Na+/K+-ATPase.

By Suvarchala Avvari, Revathi Chapa, Jeffry Adiwidjaja, Rebecca Graves, Viera Lukacova

American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 20-23, 2024, Salt Lake City, Utah