Modeling Effects of Exenatide on the Pharmacokinetics of Acetaminophen, Digoxin, and Warfarin

Authors: Fraczkiewicz G, Parrott N, Lavé T, Lukacova V, Bolger MB, Crison JR, Woltosz WS
Conference: AAPS
Keywords: absorption, absorption model, exenatide, permeability, Type 2 diabetes
Software: ADMET Predictor®, GastroPlus®

Objectives

Exenatide, a 39-amino acid peptide used for treatment of type 2 diabetes, is known to inhibit gastric emptying and as a result to alter the absorption of orally administered concomitant medications. After subcutaneous administration, exenatide is rapidly absorbed, usually reaching peak concentrations 2 hours postadministration. It is eliminated renally with a 2.5 hr half-life. The aim of our study was to build a model of delayed gastric emptying caused by exenatide that could be applied to any drug co-administered with it, and would allow predicting its effect on the drug’s pharmacokinetics.

American Association of Pharmaceutical Scientists (AAPS), November 17-19, 2008, Atlanta, GA

By Grazyna Fraczkiewicz, Neil Parrott, Thierry Lave, Viera Lukacova, Michael B. Bolger, John R. Crison, & Walter S. Woltosz