Health AI Central
Peer-Reviewed Publication
Eur J Pharm Sci2026;107691.October 16, 2026Journal Article

Translational Evaluation of In Vitro-to-In Vivo Extrapolation Techniques for Brain Penetration Using Open Flow Microperfusion and Microdialysis in Rats.

Yukiko Murata1, Janita Hogan2, Zubida M Al-Majdoub3, Jonathan Cheong4, Jingjing Guo1, Kunihiko Mizuno5, Tom De Bruyn6, Raymond Evers7, Thomas Altendorfer-Kroath8, Cornelis E C A Hop4, Anne Kanta9, Megan Turski10, Michael A Zientek11, Sibylle Neuhoff12, Thomas Birngruber8, Aleksandra Galetin3, Amin Rostami-Hodjegan13, Kayode Ogungbenro14
1Tanabe Pharma Corporation, Kanagawa, Japan.
2Merck & Co., Inc., Rahway, NJ, USA.
3Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
4Genentech Inc, South San Francisco, California, USA.
5Takeda Pharmaceuticals Limited, San Diego, California, USA.
6Genentech Inc, South San Francisco, California, USA.; Johnson & Johnson, Preclinical Sciences and Translational Safety, La Jolla, California, USA.
7Johnson & Johnson, Preclinical Sciences and Translational Safety, Springhouse, Pennsylvania, USA.
8JOANNEUM RESEARCH - HEALTH - Institute for Biomedical Research and Technologies, Graz, Austria.
9Takeda Pharmaceuticals Limited, San Diego, California, USA; Genesis Therapeutics, San Diego, California.
10Takeda Pharmaceuticals Limited, San Diego, California, USA; Neurocrine Biosciences, San Diego, California.
11Takeda Pharmaceuticals Limited, San Diego, California, USA; Treeline Biosciences, San Diego, California.
12Certara UK Ltd., MID3, Sheffield, United Kingdom.
13Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Certara UK Ltd., MID3, Sheffield, United Kingdom.
14Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.. Electronic address: kayode.ogungbenro@manchester.ac.uk.
PubMed DOI

Abstract

There is a growing need to leverage mathematical models of the central nervous system (CNS) with translational approaches employing in vitro-in vivo extrapolation (IVIVE) approaches. As a benchmark of brain penetration, unbound brain partitioning (Kp,uu), and subsequently a combination of cerebral Open Flow Microperfusion (cOFM) and microdialysis (MD) were evaluated in rats. Additionally, a six-co…

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