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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”
Author(s) -
Won Christina S.,
Lan Tian,
VanderMolen Karen M.,
Dawson Paul A.,
Oberlies Nicholas H.,
Widmer Wilbur W.,
Scarlett Yolanda V.,
Paine Mary F.
Publication year - 2013
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.136
Subject(s) - grapefruit juice , fexofenadine , terfenadine , chemistry , organic anion transporting polypeptide , pharmacology , citrus paradisi , naringin , pharmacokinetics , crossover study , bioavailability , food science , in vivo , chromatography , biochemistry , transporter , medicine , microbiology and biotechnology , biology , alternative medicine , pathology , rutaceae , horticulture , gene , placebo
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.