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IMI - oral biopharm...
IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1 : Characterisation of the OrBiTo database of compounds
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- Margolskee, Alison (author)
- Univ Manchester, Manchester M13 9PL, Lancs, England
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- Darwich, Adam S. (author)
- Univ Manchester, Manchester M13 9PL, Lancs, England
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- Pepin, Xavier (author)
- AstraZeneca, London, England;Sanofi, Paris, France
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- Pathak, Shriram M. (author)
- Simcyp Ltd, Sheffield, S Yorkshire, England
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- Bolger, Michael B. (author)
- Simulat Plus Inc, Lancaster, CA USA
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- Aarons, Leon (author)
- Univ Manchester, Manchester M13 9PL, Lancs, England
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- Rostami-Hodjegan, Amin (author)
- Simcyp Ltd, Sheffield, S Yorkshire, England;Univ Manchester, Manchester M13 9PL, Lancs, England
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- Angstenberger, Jonas (author)
- AbbVie, Wiesbaden, Germany
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- Graf, Franziska (author)
- AbbVie, Wiesbaden, Germany
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- Laplanche, Loic (author)
- AbbVie, Wiesbaden, Germany
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- Mueller, Thomas (author)
- AbbVie, Wiesbaden, Germany
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- Carlert, Sara (author)
- AstraZeneca, Gothenburg, Sweden
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- Daga, Pankaj (author)
- AstraZeneca, New York, NY USA
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- Murphy, Donal (author)
- AstraZeneca, London, England
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- Tannergren, Christer (author)
- AstraZeneca, Gothenburg, Sweden
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- Yasin, Mohammed (author)
- AstraZeneca, London, England
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- Greschat-Schade, Susanne (author)
- Bayer Pharma AG, Berlin, Germany
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- Mueck, Wolfgang (author)
- Bayer Pharma AG, Berlin, Germany
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- Muenster, Uwe (author)
- Bayer Pharma AG, Berlin, Germany
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- van der Mey, Dorina (author)
- Bayer Pharma AG, Berlin, Germany
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- Frank, Kerstin Julia (author)
- Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
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- Lloyd, Richard (author)
- GlaxoSmithKline, Brentford, Middx, England
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- Adriaenssen, Lieve (author)
- Janssen, Beerse, Belgium
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- Bevernage, Jan (author)
- Janssen, Beerse, Belgium
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- De Zwart, Loeckie (author)
- Janssen, Beerse, Belgium
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- Swerts, Dominique (author)
- Janssen, Beerse, Belgium
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- Tistaert, Christophe (author)
- Janssen, Beerse, Belgium
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- Van Den Bergh, An (author)
- Janssen, Beerse, Belgium
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- Van Peer, Achiel (author)
- Janssen, Beerse, Belgium
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- Beato, Stefania (author)
- Novartis, Basel, Switzerland
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Nguyen-Trung, Anh-Thu (author)
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- Bennett, Joanne (author)
- Pfizer, Tadworth, Middx, England
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- McAllister, Mark (author)
- Pfizer, Tadworth, Middx, England
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- Wong, Mei (author)
- Pfizer, Tadworth, Middx, England
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- Zane, Patricia (author)
- Sanofi, Bridgewater, NJ USA
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- Ollier, Celine (author)
- Sanofi, Paris, France
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- Vicat, Pascale (author)
- Sanofi, Paris, France
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- Kolhmann, Markus (author)
- Sanofi, Frankfurt, Germany
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- Marker, Alexander (author)
- Sanofi, Paris, France
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- Brun, Priscilla (author)
- Sanofi, Paris, France
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- Mazuir, Florent (author)
- Sanofi, Paris, France
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- Beilles, Stephane (author)
- Sanofi, Paris, France
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- Venczel, Marta (author)
- Sanofi, Frankfurt, Germany
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- Boulenc, Xavier (author)
- Sanofi, Paris, France
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- Loos, Petra (author)
- Sanofi, Frankfurt, Germany
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- Lennernäs, Hans (author)
- Uppsala universitet,Institutionen för farmaci
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- Abrahamsson, Bertil (author)
- AstraZeneca, Gothenburg, Sweden
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 598-609
- Related links:
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https://www.research...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- Physiologically-based pharmacokinetics (PBPK)
- Modelling and simulation (M&S)
- Absorption
- Oral bioavailability (F-oral)
- Biopharmaceutics
- Drug database
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
- Articles in the publication
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European Journal ...
- By the university
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Uppsala University