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Can a monthly exenatide extended release regimen provide a therapeutic and cost benefit?
Author(s) -
Elkeeb Rania,
Eid Tony,
Yu Janie,
Nguyen Hang,
Atef Eman
Publication year - 2021
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2279
Subject(s) - exenatide , physiologically based pharmacokinetic modelling , regimen , extended release , pharmacokinetics , pharmacology , medicine , plasma concentration , diabetes mellitus , endocrinology , type 2 diabetes
Exenatide is used to treat type 2 diabetes mellitus. The current regimen is a 2 mg extended release (ER) weekly injection. The aim of our study was to prove the efficacy of exenatide ER if administered once‐monthly. 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. (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 exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Our simulation from Excel and Simcyp ® showed that the drug plasma levels of the once monthly ER dose maintained a steady state concentration (C ss ) above the MEC. The simulated Excel plasma level ranged from C min to C max of 60–130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the C ss of the ER monthly dose. The Simcyp® simulated C ss of the ER was 117 ng/L. A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could well improve patient adherence.