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The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers


Crowe, A and Wright, C, The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers, Xenobiotica: The Fate of Foreign Compounds in Biological Systems, 42, (6) pp. 538-549. ISSN 0049-8254 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 Informa UK, Ltd.

DOI: doi:10.3109/00498254.2011.643256


1. Caco-2 cells were used to compare P-gp mediated efflux and passive permeability using bidirectional transport of 11 antihistamines. An efflux ratio >2 indicated active efflux, with PSC833 and GF120918 used as functional P-gp inhibitors.

2. Antihistamines were measured directly by HPLC or LC/MS.

3. Fexofenadine had an efflux ratio of 37, yet had negligible passive permeability, even in the presence of a pH gradient (0.1  106 cm/sec). Its precursor, terfenadine, had an efflux ratio of 2.5, while cetirizine, desloratadine and hydroxyzine were 4, 7 and 14, respectively. After incubation with P-gp inhibitors, these ratios dropped significantly. Loratadine, by contrast, had equivalent transport in both directions and passive permeability was high (24  106 cm/sec). Dimenhydrinate was the only other sedating antihistamine to exhibit efflux, with a ratio of 10.

4. Gradient conditions of pH (6/7.4) increased efflux of terfenadine and desloratadine to over 31 and 38 fold respectively, yet this increased efflux was not associated with P-gp.

5. Altering functional P-gp in the gut is likely to influence absorption of some sedating antihistamines such as dimenhydrinate and hydroxyzine and most less-sedating antihistamines except loratadine. In addition, desloratadine exhibits pH dependent efflux which could further induce variable absorption of this antihistamine.

Item Details

Item Type:Refereed Article
Keywords:P-glycoprotein, intestinal absorption, fexofenadine, cetirizine, pH dependent transport
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Basic Pharmacology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Wright, C (Mr Carl Wright)
ID Code:92571
Year Published:2012
Web of Science® Times Cited:9
Deposited By:Pharmacy
Deposited On:2014-06-23
Last Modified:2014-10-09

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