Application of modelling of cell monolayer permeation data to generate input parameters compatible with in vitro-in vivo translation of blood-brain-barrier disposition of drugs.

Janita Hogan¹, Yukiko Murata², Zubida M Al-Majdoub³, Jonathan Cheong⁴, Jingjing Guo¹, Kunihiko Mizuno⁵, Tom De Bruyn⁶, Cornelis E C A Hop⁴, Raymond Evers⁷, Anne Kanta⁸, Mike Zientek⁹, Sibylle Neuhoff¹⁰, Aleksandra Galetin³, Amin Rostami-Hodjegan¹¹, Kayode Ogungbenro¹²

¹Merck & Co., Inc., Rahway, NJ, USA.

²Mitsubishi Tanabe Pharma, Corporation, Kanagawa, Japan.

³Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom.

⁴Genentech Inc, South San Francisco, CA, USA.

⁵Takeda Pharmaceuticals Limited, San Diego, CA, USA.

⁶Genentech Inc, South San Francisco, CA, USA; Current address: Johnson & Johnson, Preclinical Sciences and Translational Safety, La Jolla, CA, (Current address), USA.

⁷Johnson & Johnson, Preclinical Sciences and Translational Safety, Springhouse, PA, USA.

⁸Takeda Pharmaceuticals Limited, San Diego, CA, USA; Current address: Genesis Therapeutics, San Diego, CA, USA.

⁹Takeda Pharmaceuticals Limited, San Diego, CA, USA; Current address: Treeline Biosciences, San Diego, CA, USA.

¹⁰Certara Predictive Technologies, Sheffield, UK.

¹¹Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom; Certara Predictive Technologies, Sheffield, UK.

¹²Centre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom. Electronic address: kayode.ogungbenro@manchester.ac.uk.

PubMed DOI

Abstract

Adequate translation of parameters from in vitro experiments to in vivo requires a proper characterisation and mechanistic representation of the systems. The aim of this study was to apply a mechanistic model to better characterise the data from experiments involving in vitro cell lines transfected with ABCB1 genes. In vitro bi-directional transport data (compound recoveries, apparent permeabiliti…

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Mentioned Companies

MeSH Terms

Animals0Dogs0Blood-Brain Barrier*Madin Darby Canine Kidney Cells0Humans0Models, Biological*Swine0LLC-PK1 Cells0Pharmaceutical Preparations0ATP Binding Cassette Transporter, Subfamily B, Member 10Cell Line0ATP Binding Cassette Transporter, Subfamily B0Biological Transport0Permeability0Cell Membrane Permeability0Rats0

Keywords

Blood-brain-barrierIn vitroMechanisticModellingP-glycoproteinTransporters

Article Info

PMID: 41740806
DOI: 10.1016/j.ejps.2026.107486
Received: November 4, 2025
Accepted: February 23, 2026

How to Cite

Hogan J et al. Application of modelling of cell monolayer permeation data to generate input parameters compatible with in vitro-in vivo translation of blood-brain-barrier disposition of drugs. Eur J Pharm Sci2026;220107486. doi:10.1016/j.ejps.2026.107486

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