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IMI - Oral biopharm...
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Darwich, Adam S.Univ Manchester, Manchester M13 9PL, Lancs, England
(author)
IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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Elsevier BV,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-361078
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-361078URI
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https://doi.org/10.1016/j.ejps.2016.09.037DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Margolskee, AlisonUniv Manchester, Manchester M13 9PL, Lancs, England
(author)
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Pepin, XavierAstraZeneca, London, England;Sanofi, Paris, France
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Aarons, LeonUniv Manchester, Manchester M13 9PL, Lancs, England
(author)
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Galetin, AleksandraUniv Manchester, Manchester M13 9PL, Lancs, England
(author)
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Rostami-Hodjegan, AminUniv Manchester, Manchester M13 9PL, Lancs, England;Simcyp Ltd, Sheffield, S Yorkshire, England
(author)
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Carlert, SaraAstraZeneca, Gothenburg, Sweden
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Hammarberg, MariaAstraZeneca, Gothenburg, Sweden
(author)
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Hilgendorf, ConstanzeAstraZeneca, Gothenburg, Sweden
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Johansson, PernillaAstraZeneca, Gothenburg, Sweden
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Karlsson, EvaAstraZeneca, Gothenburg, Sweden
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Murphy, DonalAstraZeneca, London, England
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Tannergren, ChristerAstraZeneca, Gothenburg, Sweden
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Thorn, HelenaAstraZeneca, Gothenburg, Sweden
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Yasin, MohammedAstraZeneca, London, England
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Mazuir, FlorentSanofi, Paris, France
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Nicolas, OlivierSanofi, Paris, France
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Ramusovic, SergejSanofi, Frankfurt, Germany
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Xu, ChristineSanofi, Bridgewater, NJ USA
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Pathak, Shriram M.Simcyp Ltd, Sheffield, S Yorkshire, England
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Korjamo, TimoOrion Pharma, Espoo, Finland
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Laru, JohannaOrion Pharma, Espoo, Finland;AstraZeneca, London, England
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Malkki, JussiOrion Pharma, Espoo, Finland
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Pappinen, SariOrion Pharma, Espoo, Finland
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Tuunainen, JohannaOrion Pharma, Espoo, Finland
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Dressman, JenniferGoethe Univ Frankfurt Am Main, Frankfurt, Germany
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Hansmann, SimoneGoethe Univ Frankfurt Am Main, Frankfurt, Germany
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Kostewicz, EdmundGoethe Univ Frankfurt Am Main, Frankfurt, Germany
(author)
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He, HandanNovartis, New York, NY USA
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Heimbach, TychoNovartis, New York, NY USA
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Wu, FanNovartis, New York, NY USA
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Hoft, CarolinAbbVie, Wiesbaden, Germany
(author)
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Pang, YanAbbVie, Wiesbaden, Germany
(author)
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Bolger, Michael B.Simulat Plus Inc, Lancaster, CA USA
(author)
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Huehn, EvaSimulat Plus Inc, Lancaster, CA USA
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Lukacova, VieraSimulat Plus Inc, Lancaster, CA USA
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Mullin, James M.Simulat Plus Inc, Lancaster, CA USA
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Szeto, Ke X.Simulat Plus Inc, Lancaster, CA USA
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Costales, ChesterPfizer, New York, NY USA
(author)
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Lin, JianPfizer, New York, NY USA
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McAllister, MarkPfizer, Tadworth, Middx, England
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Modi, SwetaPfizer, New York, NY USA
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Rotter, CharlesPfizer, New York, NY USA
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Varma, ManthenaPfizer, Tadworth, Middx, England
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Wong, MeiPfizer, Tadworth, Middx, England
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Mitra, AmitavaMerck Sharp & Dohme Ltd, Hoddesdon, Herts, England
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Bevernage, JanJanssen, Beerse, Belgium
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Biewenga, JeikeJanssen, Beerse, Belgium
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Van Peer, AchielJanssen, Beerse, Belgium
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Lloyd, RichardGlaxoSmithKline, Brentford, Middx, England
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Shardlow, CaroleGlaxoSmithKline, Brentford, Middx, England
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Langguth, PeterJohannes Gutenberg Univ Mainz, Mainz, Germany
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Mishenzon, IrinaJohannes Gutenberg Univ Mainz, Mainz, Germany
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Nguyen, Mai Anh
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Brown, JonathanBristol Myers Squibb, Uxbridge, Middx, England
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Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn
(author)
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Abrahamsson, BertilAstraZeneca, Gothenburg, Sweden
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Univ Manchester, Manchester M13 9PL, Lancs, EnglandAstraZeneca, London, England;Sanofi, Paris, France
(creator_code:org_t)
Related titles
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In:European Journal of Pharmaceutical Sciences: Elsevier BV96, s. 626-6420928-09871879-0720
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- By the author/editor
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Darwich, Adam S.
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Margolskee, Alis ...
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Pepin, Xavier
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Aarons, Leon
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Galetin, Aleksan ...
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Rostami-Hodjegan ...
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show more...
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Carlert, Sara
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Hammarberg, Mari ...
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Hilgendorf, Cons ...
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Johansson, Perni ...
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Karlsson, Eva
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Murphy, Donal
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Tannergren, Chri ...
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Thorn, Helena
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Yasin, Mohammed
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Mazuir, Florent
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Nicolas, Olivier
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Ramusovic, Serge ...
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Xu, Christine
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Pathak, Shriram ...
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Korjamo, Timo
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Laru, Johanna
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Malkki, Jussi
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Pappinen, Sari
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Tuunainen, Johan ...
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Dressman, Jennif ...
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Hansmann, Simone
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Kostewicz, Edmun ...
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He, Handan
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Heimbach, Tycho
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Wu, Fan
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Hoft, Carolin
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Pang, Yan
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Bolger, Michael ...
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Huehn, Eva
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Lukacova, Viera
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Mullin, James M.
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Szeto, Ke X.
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Costales, Cheste ...
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Lin, Jian
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McAllister, Mark
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Modi, Sweta
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Rotter, Charles
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Varma, Manthena
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Wong, Mei
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Mitra, Amitava
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Bevernage, Jan
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Biewenga, Jeike
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Van Peer, Achiel
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Lloyd, Richard
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Shardlow, Carole
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Langguth, Peter
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Mishenzon, Irina
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Nguyen, Mai Anh
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Brown, Jonathan
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Lennernäs, Hans
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Abrahamsson, Ber ...
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