Can a monthly exenatide extended release regimen provide a therapeutic and cost benefit?

Exenatide is used to treat Type 2 Diabetes Mellitus. The current regimen is a 2mg extended release (ER) weekly injection. The aim of our study is to prove the efficacy of exenatide ER if administered once-monthly. Method The proposed monthly dose was based on an excel simulation using pharmacokinetic parameters extracted using Plot Digitizer® (version 2.6.8) from Cirincione et al (Cirincione et al., 2017), as well as accounting for the exenatide ER formulation characteristics, in vivo and in vitro exenatide stability. A PBPK model of exenatide molecule was developed using (Simcyp® version 19) based on data from in vitro and clinical PK studies. The model was used to confirm the excel simulation findings of the effectiveness of the exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Results Our simulation from Excel and Simcyp® showed that the drug plasma levels of the ER once monthly dose maintained a steady state concentration (Css) above the MEC. The simulated Excel plasma level was ranging from Cmin to Cmax of 60 - 130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the Css of the ER monthly dose. The Simcyp® simulated Css of the ER was 117ng/L. Conclusions A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could as well improve patient adherence. This article is protected by copyright. All rights reserved.