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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

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