Pharmacokinetics, in vitro and in vivo correlation, and efficacy of exenatide microspheres in diabetic rats. (January 2015)

• Record Type: Journal Article
• Authors: Li, Xingang; Zhao, Zhigang; Li, Liang; Zhou, Tianyan; Lu, Wei
• Is Part Of: Drug delivery. Volume 22:Number 1(2015:Jan.)
• Page Start: 86
• Page End: 93
• Publication Date: 2015-01
• Subjects: Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2013.871760
• Languages: English
• ISSNs: 1071-7544

Abstract

<abstract> <title>Abstract</title> <p>Modeling and simulation are aimed at achieving information about the behaviors of the drugs without the actual measurements and determination. The purpose of this study was to characterize the <italic>in vivo</italic> behavior of exenatide microspheres using model-based methods. Exenatide is a glucagon-like peptide-1 agonist medication, belonging to the group of incretin mimetics, approved for the treatment of diabetes mellitus type 2. An oil-in-water solvent evaporation method was used to prepare the exenatide microspheres and their physicochemical features were investigated. After subcutaneous injection of exenatide microspheres to streptozotocin-induced diabetic rats, the exenatide concentrations increased and kept increasing and the blood glucose decreased in all diabetic rats. The <italic>in vivo</italic> release behavior of exenatide from microspheres was described by a transit compartment model. Based on the transit compartment model, the simulation method was proposed for the description of <italic>in vivo</italic> release. The <italic>in vitro</italic> and <italic>in vivo</italic> correlation (IVIVC) was established by the model-based simulation (<italic>R</italic><sup>2</sup> = 0.903) and deconvolution (<italic>R</italic><sup>2</sup> = 0.922) methods successfully. Using a transit compartment model to characterize the <italic>in vivo</italic> exenatide release from microspheres is an acceptable approach, and the IVIVC can be estimated reliably with the model-based simulation method.</p> </abstract>