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Quantifying the impact of transporters on cellular drug permeability.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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2015 (English)In: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 35, no 5, 255-262 p.Article in journal (Refereed) Published
Abstract [en]

The conventional model of drug permeability has recently been challenged. An alternative model proposes that transporter-mediated flux is the sole mechanism of cellular drug permeation, instead of existing in parallel with passive transmembrane diffusion. We examined a central assumption of this alternative hypothesis; namely, that transporters can give rise to experimental observations that would typically be explained with passive transmembrane diffusion. Using systems-biology simulations based on available transporter kinetics and proteomic expression data, we found that such observations are possible in the absence of transmembrane diffusion, but only under very specific conditions that rarely or never occur for known human drug transporters.

Place, publisher, year, edition, pages
2015. Vol. 35, no 5, 255-262 p.
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Pharmacology and Toxicology
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URN: urn:nbn:se:uu:diva-248117DOI: 10.1016/j.tips.2015.02.009ISI: 000355045200001PubMedID: 25799456OAI: oai:DiVA.org:uu-248117DiVA: diva2:798810
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04Bibliographically approved

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Matsson, PärLundquist, PatrikArtursson, Per

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