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

Pharmaceutics

Marie Brännström¹  Pär Nordell²  Britta Bonn¹  Andrew M. Davis¹  Anna-Pia Palmgren¹  Constanze Hilgendorf²  Katarina Rubin¹  Ken Grime¹ 

[1] Respiratory, Inflammation and Autoimmunity Innovative Medicine, AstraZeneca R&D Gothenburg, 431 83 Mölndal, Sweden; E-Mails:;Drug Safety and Metabolism, AstraZeneca R&D Gothenburg, 431 83 Mölndal, Sweden; E-Mails:

关键词: montelukast;    OATP2B1;    OATP1B1;    hepatic uptake;    transporters;   

DOI  :  10.3390/pharmaceutics7040554

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.