A Modified Grapefruit Juice Eliminates Two Compound Classes as Major Mediators of the Grapefruit Juice–Fexofenadine Interaction: An In Vitro–In Vivo “Connect”

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

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 Cmax 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.

Additional Information

The Journal of Clinical Pharmacology, 53(9), 982–990
Language: English
Date: 2013
clinical pharmacology, clinical research, gastrointestinal, pharmacokinetics, drug metabolism

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