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Input estimation for extended-release formulations exemplified with exenatide
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Trägårdh, Magnus, Chappell, M. J. (Michael J.), Palm, Johan E., Evans, Neil D., Janzén, David and Gennemark, Peter (2017) Input estimation for extended-release formulations exemplified with exenatide. Frontiers in Bioengineering and Biotechnology , 5 . doi:10.3389/fbioe.2017.00024 ISSN 2296-4185.
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Official URL: http://dx.doi.org/10.3389/fbioe.2017.00024
Abstract
Estimating the in vivo absorption profile of a drug is essential when developing extended-release medications. Such estimates can be obtained by measuring plasma concentrations over time and inferring the absorption from a model of the drug’s pharmacokinetics. Of particular interest is to predict the bioavailability—the fraction of the drug that is absorbed and enters the systemic circulation. This paper presents a framework for addressing this class of estimation problems and gives advice on the choice of method. In parametric methods, a model is constructed for the absorption process, which can be difficult when the absorption has a complicated profile. Here, we place emphasis on non-parametric methods that avoid making strong assumptions about the absorption. A modern estimation method that can address very general input-estimation problems has previously been presented. In this method, the absorption profile is modeled as a stochastic process, which is estimated using Markov chain Monte Carlo techniques. The applicability of this method for extended-release formulation development is evaluated by analyzing a dataset of Bydureon, an injectable extended-release suspension formulation of exenatide, a GLP-1 receptor agonist for treating diabetes. This drug is known to have non-linear pharmacokinetics. Its plasma concentration profile exhibits multiple peaks, something that can make parametric modeling challenging, but poses no major difficulties for non-parametric methods. The method is also validated on synthetic data, exploring the effects of sampling and noise on the accuracy of the estimates.
Item Type: | Journal Article | ||||||
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Subjects: | R Medicine > RM Therapeutics. Pharmacology | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | ||||||
Library of Congress Subject Headings (LCSH): | Pharmacokinetics, Bioavailability, Drugs--Dose-response relationship | ||||||
Journal or Publication Title: | Frontiers in Bioengineering and Biotechnology | ||||||
Publisher: | Frontiers Research Foundation | ||||||
ISSN: | 2296-4185 | ||||||
Official Date: | 19 April 2017 | ||||||
Dates: |
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Volume: | 5 | ||||||
DOI: | 10.3389/fbioe.2017.00024 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 20 April 2017 | ||||||
Date of first compliant Open Access: | 21 April 2017 | ||||||
Funder: | Seventh Framework Programme (European Commission) (FP7) | ||||||
Grant number: | 316736 | ||||||
Is Part Of: | Marie Curie FP7 People ITN European Industrial Doctorate (EID) project, IMPACT (Innovative Modelling for Pharmacological Advances through Collaborative Training). Project Number: 316736. |
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