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A modified grapefruit juice eliminates two compound classes as major mediators of the grapefruit juice-fexofenadine interaction: an in vitro-in vivo "connect".


ABSTRACT: The grapefruit juice (GFJ)-fexofenadine interaction involves inhibition of intestinal organic anion transporting polypeptide (OATP)-mediated uptake. Only naringin has been shown clinically to inhibit intestinal OATP; other constituents have not been evaluated. The effects of a modified GFJ devoid of furanocoumarins (~99%) and polymethoxyflavones (~90%) on fexofenadine disposition were compared to effects of the original juice. Extracts of both juices inhibited estrone 3-sulfate and fexofenadine uptake by similar extents in OATP-transfected cells (~50% and ~25%, respectively). Healthy volunteers (n = 18) were administered fexofenadine (120 mg) with water, GFJ, or modified GFJ (240 mL) by randomized, three-way crossover design. Compared to water, both juices decreased fexofenadine geometric mean AUC and C(max) by ~25% (P ? .008 and P ? .011, respectively), with no effect on terminal half-life (P = .11). Similar effects by both juices on fexofenadine pharmacokinetics indicate furanocoumarins and polymethoxyflavones are not major mediators of the GFJ-fexofenadine interaction.

SUBMITTER: Won CS 

PROVIDER: S-EPMC4029847 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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A modified grapefruit juice eliminates two compound classes as major mediators of the grapefruit juice-fexofenadine interaction: an in vitro-in vivo "connect".

Won Christina S CS   Lan Tian T   Vandermolen Karen M KM   Dawson Paul A PA   Oberlies Nicholas H NH   Widmer Wilbur W WW   Scarlett Yolanda V YV   Paine Mary F MF  

Journal of clinical pharmacology 20130723 9


The grapefruit juice (GFJ)-fexofenadine interaction involves inhibition of intestinal organic anion transporting polypeptide (OATP)-mediated uptake. Only naringin has been shown clinically to inhibit intestinal OATP; other constituents have not been evaluated. The effects of a modified GFJ devoid of furanocoumarins (~99%) and polymethoxyflavones (~90%) on fexofenadine disposition were compared to effects of the original juice. Extracts of both juices inhibited estrone 3-sulfate and fexofenadine  ...[more]

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