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Pharmaceutics 2015, 7(4), 554-564; doi:10.3390/pharmaceutics7040554

Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells

1
Respiratory, Inflammation and Autoimmunity Innovative Medicine, AstraZeneca R&D Gothenburg, 431 83 Mölndal, Sweden
2
Drug Safety and Metabolism, AstraZeneca R&D Gothenburg, 431 83 Mölndal, Sweden
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Afzal R. Mohammed
Received: 15 September 2015 / Revised: 24 November 2015 / Accepted: 9 December 2015 / Published: 15 December 2015
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Abstract

Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Montelukast is a carboxylic acid, a relatively potent inhibitor of OATP1B1, OATP1B3, and OATP2B1, and has previously been postulated to be actively transported into human hepatocytes. Using OATP1B1-transfected HEK293 cells and primary human hepatocytes in the presence of OATP inhibitors we demonstrate for the first time that active OATP-dependent transport is unlikely to play a significant role in the human disposition of montelukast. View Full-Text
Keywords: montelukast; OATP2B1; OATP1B1; hepatic uptake; transporters montelukast; OATP2B1; OATP1B1; hepatic uptake; transporters
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Brännström, M.; Nordell, P.; Bonn, B.; Davis, A.M.; Palmgren, A.-P.; Hilgendorf, C.; Rubin, K.; Grime, K. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells. Pharmaceutics 2015, 7, 554-564.

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