Effect of fruit juices on the oral bioavailability of fexofenadine in rats

J Pharm Sci. 2005 Feb;94(2):233-9. doi: 10.1002/jps.20231.


Fexofenadine has been identified as a substrate for both the efflux transporter, P-glycoprotein (P-gp), as well as the influx transporter, organic anion transporting polypeptide (OATP). Clinical studies in humans showed that fruit juices reduced the oral bioavailability of fexofenadine by preferentially inhibiting OATP over P-gp. The objective of this study was to investigate the effects of fruit juices on the oral absorption of fexofenadine in rats to establish a preclinical fruit juice-drug interaction model. In rats, fexofenadine was excreted unchanged in the urine, bile, and gastrointestinal tract, indicating minimal metabolism, making it an ideal probe to study transport processes. Coadministration of fexofenadine with ketoconazole, a P-gp inhibitor, increased the oral exposure of fexofenadine by 187%. In contrast, coadministration of fexofenadine with orange juice or apple juice to rats decreased the oral exposure of fexofenadine by 31 and 22%, respectively. Increasing the quantity of orange or apple juice administered further decreased the oral exposure of fexofenadine, by 40 and 28%, respectively. This reduction in fexofenadine bioavailability was moderate compared to that seen in humans. These findings suggest that in rats fruit juices may also preferentially inhibit OATP rather than P-gp-mediated transport in fexofenadine oral absorption, albeit to a lesser extent than observed in humans. This fruit juice--drug interaction rat model may be useful in prediction of potential food--drug interactions in humans for drug candidates.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Beverages / adverse effects*
  • Biological Availability
  • Citrus
  • Food-Drug Interactions / physiology*
  • Fruit*
  • Histamine H1 Antagonists / pharmacokinetics*
  • Intestinal Absorption
  • Male
  • Malus
  • Organic Anion Transporters / antagonists & inhibitors*
  • Organic Anion Transporters / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Terfenadine / analogs & derivatives*
  • Terfenadine / pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B
  • Histamine H1 Antagonists
  • Organic Anion Transporters
  • Terfenadine
  • fexofenadine