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Unbound Brain-to-Pl...
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Loryan, Irena,Associate Professor (Docent),1977-Uppsala universitet,Institutionen för farmaci
(author)
Unbound Brain-to-Plasma Partition Coefficient, K-p,K-uu,K-brain-a Game Changing Parameter for CNS Drug Discovery and Development
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-04-11
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Springer Nature,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-485648
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485648URI
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https://doi.org/10.1007/s11095-022-03246-6DOI
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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Purpose More than 15 years have passed since the first description of the unbound brain-to-plasma partition coefficient (K-p,K-uu,K-brain) by Prof. Margareta Hammarlund-Udenaes, which was enabled by advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support the notion that the unbound (free) concentration of a drug at the site of action, such as the brain, is the driving force for pharmacological responses. Towards this end, K-p,K-uu,K-brain is the key parameter to obtain unbound brain concentrations from unbound plasma concentrations. Methods To understand the importance and impact of the K-p,K-uu,K-brain concept in contemporary drug discovery and development, a survey has been conducted amongst major pharmaceutical companies based in Europe and the USA. Here, we present the results from this survey which consisted of 47 questions addressing: 1) Background information of the companies, 2) Implementation, 3) Application areas, 4) Methodology, 5) Impact and 6) Future perspectives. Results and conclusions From the responses, it is clear that the majority of the companies (93%) has established a common understanding across disciplines of the concept and utility of K-p,K-uu,K-brain as compared to other parameters related to brain exposure. Adoption of the K-p,K-uu,K-brain concept has been mainly driven by individual scientists advocating its application in the various companies rather than by a top-down approach. Remarkably, 79% of all responders describe the portfolio impact of K-p,K-uu,K-brain implementation in their companies as 'game-changing'. Although most companies (74%) consider the current toolbox for K-p,K-uu,K-brain assessment and its validation satisfactory for drug discovery and early development, areas of improvement and future research to better understand human brain pharmacokinetics/pharmacodynamics translation have been identified.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Reichel, AndreasBayer AG, Pharma R&D, DMPK M&S, Berlin, Germany.
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Feng, BoVertex Pharmaceut, DMPK, Boston, MA 02210 USA.
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Bundgaard, ChristofferH Lundbeck & Co AS, Translat DMPK, Copenhagen, Denmark.
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Shaffer, ChristopherBiogen Inc, External Innovat Res & Dev, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
(author)
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Kalvass, CoryAbbVie Inc, DMPK BA, N Chicago, IL USA.
(author)
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Bednarczyk, DallasNovartis Inst BioMed Res, Pharmacokinet Sci, Cambridge, MA USA.
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Morrison, DeniseJanssen Res & Dev, DMPK, Beerse, Belgium.
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Lesuisse, DominiqueSanofi, Rare & Neurol Dis, Chilly Mazarin, France.
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Hoppe, EdmundBoehringer Ingelheim Pharma GmbH & Co KG, DMPK, Biberach, Germany.
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Terstappen, Georg C.Cambrian Biopharma, New York, NY USA.
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Fischer, HolgerRoche Innovat Ctr Basel, Roche Pharma Res & Early Dev, Translat PK PD & Clin Pharmacol Pharmaceut Sci, Basel, Switzerland.
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Di, LiPfizer, Worldwide Res & Dev, Pharmacokinet Dynam & Metab, Groton, CT USA.
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Colclough, NicolaAstraZeneca, Oncol R&D, Oncol DMPK, Cambridge, England.
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Summerfield, ScottGSK, Bioanal Immunogenic & Biomarkers, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
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Buckley, Stephen T.Novo Nordisk AS, Global Res Technol, Malov, Denmark.
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Maurer, Tristan S.Pfizer, Worldwide Res & Dev, Pharmacokinet Dynam & Metab, Cambridge, MA USA.
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Fridén, MarkusUppsala universitet,Institutionen för farmaci,AstraZeneca, Inhalat Prod Dev, Pharmaceut Technol & Dev, Operat, Gothenburg, Sweden.(Swepub:uu)mafri535
(author)
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Uppsala universitetInstitutionen för farmaci
(creator_code:org_t)
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In:Pharmaceutical research: Springer Nature39:7, s. 1321-13410724-87411573-904X
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Reichel, Andreas
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