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A semi-mechanistic modeling strategy for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacometrics)
AstraZeneca R&D, Mölndal, Sweden. (Pharmaceutical Development)
AstraZeneca R&D, Mölndal, Sweden.
Institute of Pharmacy, University of Greifswald, Greifswald, Germany.
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2012 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 29, no 2, 574-584 p.Article in journal (Refereed) Published
Abstract [en]


To outline and test a new modeling approach for prospective predictions of absorption from newly developed modified release formulations based on in vivo studies of gastro intestinal (GI) transit, drug release and regional absorption for the investigational drug AZD0837.


This work was a natural extension to the companion article "A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations". The drug release model governed the amount of substance released in distinct GI regions over time. GI distribution of released drug substance, region specific rate and extent of absorption and the influence of food intake were estimated. The model was informed by magnetic marker monitoring data and data from an intubation study with local administration in colon.


Distinctly different absorption properties were characterized for different GI regions. Bioavailability over the gut-wall was estimated to be high in duodenum (70%) compared to the small intestine (25%). Colon was primarily characterized by a very slow rate of absorption.


The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2012. Vol. 29, no 2, 574-584 p.
Keyword [en]
IVIVC, magnetic marker monitoring, mechanistic modeling, modified release, NONMEM
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
URN: urn:nbn:se:uu:diva-162890DOI: 10.1007/s11095-011-0595-2ISI: 000299506700021PubMedID: 21948384OAI: oai:DiVA.org:uu-162890DiVA: diva2:461910
Available from: 2011-12-06 Created: 2011-12-06 Last updated: 2012-02-24Bibliographically approved

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Bergstrand, MartinKarlsson, Mats O.
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