Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides

Clin Pharmacol Ther. 2005 Mar;77(3):170-7. doi: 10.1016/j.clpt.2004.10.005.


Objective: The purpose of this study was to elucidate the potential clinical relevance and mechanism(s) of action of 2 different volumes of grapefruit juice on the reduction of bioavailability of fexofenadine, a substrate of organic anion transporting polypeptides.

Methods: Grapefruit juice or water at normal (300 mL) or high (1200 mL) volume was ingested concomitantly with 120 mg fexofenadine by 12 healthy volunteers in a randomized 4-way crossover study, and fexofenadine pharmacokinetics were determined over a period of 8 hours.

Results: The 300-mL volume of grapefruit juice decreased the mean area under the plasma drug concentration-time curve (AUC) and the peak plasma drug concentration of fexofenadine to 58% (P < .001) and 53% (P < .001), respectively, of those with the corresponding volume of water, and 1200 mL grapefruit juice reduced these parameters to 36% ( P < .001) and 33% ( P < .001), respectively, of those with the corresponding volume of water. The 300-mL volume of grapefruit juice diminished the AUC of fexofenadine variably among individuals. This decline correlated with baseline AUC of fexofenadine with water at equivalent volume (r(2) = 0.97, P < .0001). The 1200-mL volume of grapefruit juice decreased the AUC of fexofenadine more than the 300-mL volume of grapefruit juice compared with the corresponding volume of water in each subject by a constant amount. Grapefruit juice, 300 mL and 1200 mL, reduced the coefficient of variation of the AUC of fexofenadine by 2-fold compared with that with a matching volume of water.

Conclusions: Grapefruit juice at a commonly consumed volume diminished the oral bioavailability of fexofenadine sufficiently to be pertinent clinically, likely by direct inhibition of uptake by intestinal organic anion transporting polypeptide A (OATP-A; new nomenclature, OATP1A2). A much higher volume caused an additional modest effect, possibly from reduced intestinal concentration and transit time of fexofenadine. This food-drug interaction appears to be novel and may be relevant to other fruit juices and drugs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Biological Availability
  • Citrus paradisi / physiology*
  • Cross-Over Studies
  • Drinking
  • Female
  • Food-Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Organic Anion Transporters / chemistry
  • Organic Anion Transporters / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Terfenadine / administration & dosage
  • Terfenadine / analogs & derivatives*
  • Terfenadine / blood
  • Terfenadine / pharmacokinetics*
  • Water / metabolism
  • Water / pharmacology


  • Organic Anion Transporters
  • Peptides
  • Water
  • Terfenadine
  • fexofenadine