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IMI - oral biopharm...
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Margolskee, AlisonUniv Manchester, Manchester M13 9PL, Lancs, England
(author)
IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1 : Characterisation of the OrBiTo database of compounds
- 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-361061
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-361061URI
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https://doi.org/10.1016/j.ejps.2016.09.027DOI
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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Predicting oral bioavailability (F-oral) is of importance for estimating systemic exposure of orally administered drugs. Physiologically-based pharmacokinetic (PBPK) modelling and simulation have been applied extensively in biopharmaceutics recently. The Oral Biopharmaceutical Tools (OrBiTo) project (Innovative Medicines Initiative) aims to develop and improve upon biopharmaceutical tools, including PBPK absorption models. A large-scale evaluation of PBPK models may be considered the first step. Here we characterise the OrBiTo active pharmaceutical ingredient (API) database for use in a large-scale simulation study. The OrBiTo database comprised 83 APIs and 1475 study arms. The database displayed a median logP of 3.60 (2.40-4.58), human blood-to-plasma ratio of 0.62 (0.57-0.71), and fraction unbound in plasma of 0.05 (0.01-0.17). The database mainly consisted of basic compounds (48.19%) and Biopharmaceutics Classification System class II compounds (55.81%). Median human intravenous clearance was 16.9 L/h (interquartile range: 11.6-43.6 L/h; n = 23), volume of distribution was 80.8 L (54.5-239 L; n = 23). The majority of oral formulations were immediate release (IR: 87.6%). Human Foral displayed a median of 0.415 (0.203-0.724; n = 22) for IR formulations. The OrBiTo database was found to be largely representative of previously published datasets. 43 of the APIs were found to satisfy the minimum inclusion criteria for the simulation exercise, and many of these have significant gaps of other key parameters, which could potentially impact the interpretability of the simulation outcome. However, the OrBiTo simulation exercise represents a unique opportunity to perform a large-scale evaluation of the PBPK approach to predicting oral biopharmaceutics.
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Darwich, Adam S.Univ Manchester, Manchester M13 9PL, Lancs, England
(author)
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Pepin, XavierAstraZeneca, London, England;Sanofi, Paris, France
(author)
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Pathak, Shriram M.Simcyp Ltd, Sheffield, S Yorkshire, England
(author)
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Bolger, Michael B.Simulat Plus Inc, Lancaster, CA USA
(author)
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Aarons, LeonUniv Manchester, Manchester M13 9PL, Lancs, England
(author)
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Rostami-Hodjegan, AminSimcyp Ltd, Sheffield, S Yorkshire, England;Univ Manchester, Manchester M13 9PL, Lancs, England
(author)
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Angstenberger, JonasAbbVie, Wiesbaden, Germany
(author)
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Graf, FranziskaAbbVie, Wiesbaden, Germany
(author)
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Laplanche, LoicAbbVie, Wiesbaden, Germany
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Mueller, ThomasAbbVie, Wiesbaden, Germany
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Carlert, SaraAstraZeneca, Gothenburg, Sweden
(author)
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Daga, PankajAstraZeneca, New York, NY USA
(author)
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Murphy, DonalAstraZeneca, London, England
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Tannergren, ChristerAstraZeneca, Gothenburg, Sweden
(author)
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Yasin, MohammedAstraZeneca, London, England
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Greschat-Schade, SusanneBayer Pharma AG, Berlin, Germany
(author)
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Mueck, WolfgangBayer Pharma AG, Berlin, Germany
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Muenster, UweBayer Pharma AG, Berlin, Germany
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van der Mey, DorinaBayer Pharma AG, Berlin, Germany
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Frank, Kerstin JuliaBoehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
(author)
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Lloyd, RichardGlaxoSmithKline, Brentford, Middx, England
(author)
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Adriaenssen, LieveJanssen, Beerse, Belgium
(author)
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Bevernage, JanJanssen, Beerse, Belgium
(author)
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De Zwart, LoeckieJanssen, Beerse, Belgium
(author)
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Swerts, DominiqueJanssen, Beerse, Belgium
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Tistaert, ChristopheJanssen, Beerse, Belgium
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Van Den Bergh, AnJanssen, Beerse, Belgium
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Van Peer, AchielJanssen, Beerse, Belgium
(author)
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Beato, StefaniaNovartis, Basel, Switzerland
(author)
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Nguyen-Trung, Anh-Thu
(author)
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Bennett, JoannePfizer, Tadworth, Middx, England
(author)
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McAllister, MarkPfizer, Tadworth, Middx, England
(author)
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Wong, MeiPfizer, Tadworth, Middx, England
(author)
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Zane, PatriciaSanofi, Bridgewater, NJ USA
(author)
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Ollier, CelineSanofi, Paris, France
(author)
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Vicat, PascaleSanofi, Paris, France
(author)
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Kolhmann, MarkusSanofi, Frankfurt, Germany
(author)
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Marker, AlexanderSanofi, Paris, France
(author)
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Brun, PriscillaSanofi, Paris, France
(author)
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Mazuir, FlorentSanofi, Paris, France
(author)
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Beilles, StephaneSanofi, Paris, France
(author)
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Venczel, MartaSanofi, Frankfurt, Germany
(author)
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Boulenc, XavierSanofi, Paris, France
(author)
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Loos, PetraSanofi, Frankfurt, Germany
(author)
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Lennernäs, HansUppsala universitet,Institutionen för farmaci(Swepub:uu)hanslenn
(author)
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Abrahamsson, BertilAstraZeneca, Gothenburg, Sweden
(author)
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Univ Manchester, Manchester M13 9PL, Lancs, EnglandAstraZeneca, London, England;Sanofi, Paris, France
(creator_code:org_t)
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In:European Journal of Pharmaceutical Sciences: Elsevier BV96, s. 598-6090928-09871879-0720
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Margolskee, Alis ...
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Darwich, Adam S.
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Pepin, Xavier
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Pathak, Shriram ...
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Bolger, Michael ...
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Aarons, Leon
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Rostami-Hodjegan ...
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Angstenberger, J ...
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Graf, Franziska
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Laplanche, Loic
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Mueller, Thomas
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Carlert, Sara
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Daga, Pankaj
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Murphy, Donal
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Tannergren, Chri ...
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Yasin, Mohammed
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Greschat-Schade, ...
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Mueck, Wolfgang
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Muenster, Uwe
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van der Mey, Dor ...
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Frank, Kerstin J ...
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Lloyd, Richard
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Adriaenssen, Lie ...
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Bevernage, Jan
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De Zwart, Loecki ...
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Swerts, Dominiqu ...
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Tistaert, Christ ...
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Van Den Bergh, A ...
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Van Peer, Achiel
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Beato, Stefania
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Nguyen-Trung, An ...
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Bennett, Joanne
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McAllister, Mark
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Wong, Mei
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Zane, Patricia
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Ollier, Celine
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Vicat, Pascale
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Kolhmann, Markus
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Marker, Alexande ...
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Brun, Priscilla
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Mazuir, Florent
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Beilles, Stephan ...
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Venczel, Marta
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Boulenc, Xavier
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Loos, Petra
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Lennernäs, Hans
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Abrahamsson, Ber ...
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